Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- Surendran, Praveen, Feofanova, Elena, Lahrouchi, Najim, Ntalla, Ionna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi, Cartwright, James, Hellwege, Jacklyn, Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang, Prins, Bram, Stewart, Isobel, Cabrera, Claude, Eales, James, Akbarov, Artur, Auer, Paul, Charchar, Fadi, Howson, Joanna, LifeLines Cohort, Study, Epic, C. V. D., Epic InterAct, Understanding Society Scientific, Group, Million Veteran, Program
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
- Full Text:
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- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
- Full Text:
- Reviewed:
- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
An improved 3-(4,5-dmethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl )-2H-tetrazolium proliferation assay to overcome the interference of hydralazine
- Wang, Yutang, Nguyen, Dinh, Yang, Guang, Anesi, Jack, Chai, Zhonglin, Charchar, Fadi, Golledge, Jonathan
- Authors: Wang, Yutang , Nguyen, Dinh , Yang, Guang , Anesi, Jack , Chai, Zhonglin , Charchar, Fadi , Golledge, Jonathan
- Date: 2020
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 18, no. 8 (Dec 2020), p. 379-384
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
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- Description: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p< 0.05) in the standard MTS assay, whereas microscopy suggested no change in cell numbers. Culture with 500 mu m hydralazine for 24 h increased absorbance (p< 0.05) in the standard MTS assay, however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (>= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds.
- Authors: Wang, Yutang , Nguyen, Dinh , Yang, Guang , Anesi, Jack , Chai, Zhonglin , Charchar, Fadi , Golledge, Jonathan
- Date: 2020
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 18, no. 8 (Dec 2020), p. 379-384
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p< 0.05) in the standard MTS assay, whereas microscopy suggested no change in cell numbers. Culture with 500 mu m hydralazine for 24 h increased absorbance (p< 0.05) in the standard MTS assay, however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (>= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds.
Secondary stroke prevention in polish adults: Results from the lipidogram2015 study
- Labuz-Roszak, Beata, Banach, Maciej, Skrzypek, Michal, Windak, Adam, Charchar, Fadi
- Authors: Labuz-Roszak, Beata , Banach, Maciej , Skrzypek, Michal , Windak, Adam , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 19 (2021), p.
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- Description: Background: The purpose of the study was to evaluate secondary stroke prevention in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. Material and methods: From all patients in LIPIDOGRAM2015 Study (n = 13,724), 268 subjects had a history of ischaemic stroke and were included. Results: 165 subjects (61.6%) used at least one preventive medication. Oral antiplatelet and anticoagulation agents were used by 116 (43.3%) and 70 (26.1%) patients, respectively. Only 157 (58.6%) participants used lipid-lowering drugs, and 205 (76.5%) were treated with antihypertensive drugs. Coronary heart disease (CHD) and dyslipidaemia were associated with antiplatelet treatment (p = 0.047 and p = 0.012, respectively). A history of atrial fibrillation, CHD, and previous myocardial infarction correlated with anticoagulant treatment (p = 0.001, p = 0.011, and p < 0.0001, respectively). Age, gender, time from stroke onset, place of residence, and level of education were not associated with antiplatelet or anticoagulant treatment. Only 31.7% of patients were engaged in regular physical activity, 62% used appropriate diet, and 13.6% were current smokers. Conclusions: In Poland drugs and lifestyle modification for secondary stroke prevention are not commonly adhered to. Educational programmes for physicians and patients should be developed to improve application of effective secondary prevention of stroke. © 2021 by the authors. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Labuz-Roszak, Beata , Banach, Maciej , Skrzypek, Michal , Windak, Adam , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 19 (2021), p.
- Full Text:
- Reviewed:
- Description: Background: The purpose of the study was to evaluate secondary stroke prevention in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. Material and methods: From all patients in LIPIDOGRAM2015 Study (n = 13,724), 268 subjects had a history of ischaemic stroke and were included. Results: 165 subjects (61.6%) used at least one preventive medication. Oral antiplatelet and anticoagulation agents were used by 116 (43.3%) and 70 (26.1%) patients, respectively. Only 157 (58.6%) participants used lipid-lowering drugs, and 205 (76.5%) were treated with antihypertensive drugs. Coronary heart disease (CHD) and dyslipidaemia were associated with antiplatelet treatment (p = 0.047 and p = 0.012, respectively). A history of atrial fibrillation, CHD, and previous myocardial infarction correlated with anticoagulant treatment (p = 0.001, p = 0.011, and p < 0.0001, respectively). Age, gender, time from stroke onset, place of residence, and level of education were not associated with antiplatelet or anticoagulant treatment. Only 31.7% of patients were engaged in regular physical activity, 62% used appropriate diet, and 13.6% were current smokers. Conclusions: In Poland drugs and lifestyle modification for secondary stroke prevention are not commonly adhered to. Educational programmes for physicians and patients should be developed to improve application of effective secondary prevention of stroke. © 2021 by the authors. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
The prevalence of cardiovascular risk factors and cardiovascular disease among primary care patients in Poland : results from the LIPIDOGRAM2015 study
- Jóźwiak, Jacek, Studziński, Krzysztof, Tomasik, Tomasz, Windak, Adam, Charchar, Fadi
- Authors: Jóźwiak, Jacek , Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: Atherosclerosis Supplements Vol. 42, no. (2020), p. e15-e24
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- Description: Background and aim: To estimate the prevalence of cardiovascular (CV) disease and CV risk factors among Polish patients. Methods: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the 4th quarter of 2015 and 1st and 2nd quarters of 2016; 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. Results: Nearly 19% of men and approximately 12% of women had cardiovascular disease (CVD). Over 60% of the recruited patients had hypertension (HTN), >80% had dyslipidaemia and <15% of patients were diagnosed with diabetes (DM). All of these disorders were more frequent in men. In 80% of patients the waist circumference exceed norm for the European population. Less than half of the patients were current smokers or had smoked in the past. Patients with CVD had significantly higher blood pressure and glucose levels but lower low density lipoprotein-cholesterol level. Conclusions: The prevalence of CVD and CV risk factors among patients in Poland is high. CVD is more common in men than in women. The most common CV risk factors are excess waist circumference, dyslipidaemia and HTN. Family physicians should conduct activities to prevent, diagnose early and treat CVD in the primary health care population. © 2021 Elsevier B.V. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Jóźwiak, Jacek , Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Charchar, Fadi
- Date: 2020
- Type: Text , Journal article
- Relation: Atherosclerosis Supplements Vol. 42, no. (2020), p. e15-e24
- Full Text:
- Reviewed:
- Description: Background and aim: To estimate the prevalence of cardiovascular (CV) disease and CV risk factors among Polish patients. Methods: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the 4th quarter of 2015 and 1st and 2nd quarters of 2016; 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. Results: Nearly 19% of men and approximately 12% of women had cardiovascular disease (CVD). Over 60% of the recruited patients had hypertension (HTN), >80% had dyslipidaemia and <15% of patients were diagnosed with diabetes (DM). All of these disorders were more frequent in men. In 80% of patients the waist circumference exceed norm for the European population. Less than half of the patients were current smokers or had smoked in the past. Patients with CVD had significantly higher blood pressure and glucose levels but lower low density lipoprotein-cholesterol level. Conclusions: The prevalence of CVD and CV risk factors among patients in Poland is high. CVD is more common in men than in women. The most common CV risk factors are excess waist circumference, dyslipidaemia and HTN. Family physicians should conduct activities to prevent, diagnose early and treat CVD in the primary health care population. © 2021 Elsevier B.V. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
- Breeze, Charles, Batorsky, Anna, Lee, Mi, Szeto, Mindy, Charchar, Fadi
- Authors: Breeze, Charles , Batorsky, Anna , Lee, Mi , Szeto, Mindy , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Genome Medicine Vol. 13, no. 1 (Apr 30 2021), p.
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- Reviewed:
- Description: Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
- Authors: Breeze, Charles , Batorsky, Anna , Lee, Mi , Szeto, Mindy , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Genome Medicine Vol. 13, no. 1 (Apr 30 2021), p.
- Full Text:
- Reviewed:
- Description: Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
Plasma proteomics of renal function: A transethnic meta-analysis and mendelian randomization study
- Matías-García, Pamela, Wilson, Rory, Guo, Qi, Zaghlool, Shaza, Charchar, Fadi
- Authors: Matías-García, Pamela , Wilson, Rory , Guo, Qi , Zaghlool, Shaza , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 32, no. 7 (2021), p. 1747-1763
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- Description: Background Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. Methods A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. Results In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. Conclusions In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation. © 2021 by the American Society of Nephrology
- Authors: Matías-García, Pamela , Wilson, Rory , Guo, Qi , Zaghlool, Shaza , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 32, no. 7 (2021), p. 1747-1763
- Full Text:
- Reviewed:
- Description: Background Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. Methods A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. Results In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. Conclusions In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation. © 2021 by the American Society of Nephrology
Molecular insights into genome-wide association studies of chronic kidney disease-defining traits
- Xu, Xiaoguang, Eales, James, Akbarov, Artur, Guo, Hui, Becker, Lorenz, Talavera, David, Ashraf, Fehzan, Nawaz, Jabran, Pramanik, Sanjeev, Bowes, John, Jiang, Xiao, Dormer, John, Denniff, Matthew, Antczak, Andrzej, Szulinska, Monika, Wise, Ingrid, Prestes, Priscilla, Glyda, Maciej, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Berzuini, Carlo, Woolf, Adrian, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
2020 International Society of Hypertension global hypertension practice guidelines
- Unger, Thomas, Borghi, Claudio, Charchar, Fadi, Khan, Nadia, Poulter, Neil, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Stergiou, George, Tomaszewski, Maciej, Wainford, Richard, Williams, Bryan, Schutte, Aletta
- Authors: Unger, Thomas , Borghi, Claudio , Charchar, Fadi , Khan, Nadia , Poulter, Neil , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Stergiou, George , Tomaszewski, Maciej , Wainford, Richard , Williams, Bryan , Schutte, Aletta
- Date: 2020
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 38, no. 6 (2020), p. 982-1004
- Full Text:
- Reviewed:
- Description: DOCUMENT REVIEWERS: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).
- Authors: Unger, Thomas , Borghi, Claudio , Charchar, Fadi , Khan, Nadia , Poulter, Neil , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Stergiou, George , Tomaszewski, Maciej , Wainford, Richard , Williams, Bryan , Schutte, Aletta
- Date: 2020
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 38, no. 6 (2020), p. 982-1004
- Full Text:
- Reviewed:
- Description: DOCUMENT REVIEWERS: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).
Human Y Chromosome Exerts Pleiotropic Effects on Susceptibility to Atherosclerosis
- Eales, James, Maan, Akhlaq, Xu, Xiaoguang, Michoel, Tom, Hallast, Pille, Batini, C, Zadik, Daniel, Prestes, Priscilla, Molina, Elsa, Denniff, Matthew, Schroeder, Juliane, Bjorkegren, Johan, Thompson, John, Maffia, Pasquale, Guzik, Tomasz, Keavney, Bernard, Jobling, Mark, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
- Full Text:
- Reviewed:
- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
- Full Text:
- Reviewed:
- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
The association between selected molecular biomarkers and ambulatory blood pressure patterns in African chronic kidney disease and hypertensive patients compared with normotensive controls : protocol for a longitudinal study
- Adeoye, Abiodun, Adebayo, Oladimeji, Abiola, Busayo, Iwalokun, Bamidele, Tayo, Bamidele, Charchar, Fadi, Ojo, Akinlolu, Cooper, Richard
- Authors: Adeoye, Abiodun , Adebayo, Oladimeji , Abiola, Busayo , Iwalokun, Bamidele , Tayo, Bamidele , Charchar, Fadi , Ojo, Akinlolu , Cooper, Richard
- Date: 2020
- Type: Text , Journal article
- Relation: JMIR Research Protocols Vol. 9, no. 1 (Jan 2020), p. 8
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- Reviewed:
- Description: Background: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. Objective: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. Methods: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. Results: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. Conclusions: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis.
- Authors: Adeoye, Abiodun , Adebayo, Oladimeji , Abiola, Busayo , Iwalokun, Bamidele , Tayo, Bamidele , Charchar, Fadi , Ojo, Akinlolu , Cooper, Richard
- Date: 2020
- Type: Text , Journal article
- Relation: JMIR Research Protocols Vol. 9, no. 1 (Jan 2020), p. 8
- Full Text:
- Reviewed:
- Description: Background: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. Objective: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. Methods: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. Results: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. Conclusions: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis.
Noncoding genes on sex chromosomes and their function in sex determination, dosage compensation, male traits, and diseases
- Maier, Michelle, McInerney, Molly-Rose, Graves, Jennifer, Charchar, Fadi
- Authors: Maier, Michelle , McInerney, Molly-Rose , Graves, Jennifer , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Sexual Development Vol. 15, no. 5-6 (2021), p. 432-440
- Relation: http://purl.org/au-research/grants/nhmrc/1123472
- Full Text:
- Reviewed:
- Description: The mammalian Y chromosome has evolved in many species into a specialized chromosome that contributes to sex development among other male phenotypes. This function is well studied in terms of protein-coding genes. Less is known about the noncoding genome on the Y chromosome and its contribution to both sex development and other traits. Once considered junk genetic material, noncoding RNAs are now known to contribute to the regulation of gene expression and to play an important role in refining cellular functions. The prime examples are noncoding genes on the X chromosome, which mitigate the differential dosage of genes on sex chromosomes. Here, we discuss the evolution of noncoding RNAs on the Y chromosome and the emerging evidence of how micro, long, and circular noncoding RNAs transcribed from the Y chromosome contribute to sex differentiation. We briefly touch on emerging evidence that these noncoding RNAs also contribute to some other important clinical phenotypes in humans. © 2021 S. Karger AG. All rights reserved.
- Authors: Maier, Michelle , McInerney, Molly-Rose , Graves, Jennifer , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Sexual Development Vol. 15, no. 5-6 (2021), p. 432-440
- Relation: http://purl.org/au-research/grants/nhmrc/1123472
- Full Text:
- Reviewed:
- Description: The mammalian Y chromosome has evolved in many species into a specialized chromosome that contributes to sex development among other male phenotypes. This function is well studied in terms of protein-coding genes. Less is known about the noncoding genome on the Y chromosome and its contribution to both sex development and other traits. Once considered junk genetic material, noncoding RNAs are now known to contribute to the regulation of gene expression and to play an important role in refining cellular functions. The prime examples are noncoding genes on the X chromosome, which mitigate the differential dosage of genes on sex chromosomes. Here, we discuss the evolution of noncoding RNAs on the Y chromosome and the emerging evidence of how micro, long, and circular noncoding RNAs transcribed from the Y chromosome contribute to sex differentiation. We briefly touch on emerging evidence that these noncoding RNAs also contribute to some other important clinical phenotypes in humans. © 2021 S. Karger AG. All rights reserved.
The differences in the prevalence of cardiovascular disease, its risk factors, and achievement of therapeutic goals among urban and rural primary care patients in Poland: Results from the LIPIDOGRAM 2015 study
- Studziński, Krzysztof, Tomasik, Tomasz, Windak, Adam, Banach, Maciej, Charchar, Fadi
- Authors: Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Banach, Maciej , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 23 (2021), p.
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- Reviewed:
- Description: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the years 2015 and 2016. A total of 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CVD were similar in urban and rural areas (49.5 vs. 49.4%; 13.7 vs. 13.1%; 84.2 vs. 85.2%; 14.4 vs. 14.2%, respectively). The prevalence of obesity (32.3 vs. 37.5%, p < 0.01) and excessive waist circumference (77.5 vs. 80.7%, p < 0.01), as well as abdominal obesity (p = 43.2 vs. 46.4%, p < 0.01), were higher in rural areas in both genders. Mean levels of LDL-C (128 vs. 130 mg/dL, p = 0.04) and non-HDL-C (147 vs. 148 mg/dL, p = 0.03) were slightly higher in rural populations. Altogether, 14.3% of patients with CVD from urban areas and 11.3% from rural areas reached LDL <70 mg/dL (p = 0.04). There were no important differences in the prevalence of hypertension, diabetes, dyslipidaemia, and CVD, or in mean levels of blood pressure, cholesterol fractions, glucose, and HbA1c between Polish urban and rural primary care patient populations. A high proportion of patients in cities and an even-higher proportion in rural areas did not reach the recommended targets for blood pressure, LDL-C, and HbA1c, indicating the need for novel CVD-prevention programs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Banach, Maciej , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 23 (2021), p.
- Full Text:
- Reviewed:
- Description: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the years 2015 and 2016. A total of 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CVD were similar in urban and rural areas (49.5 vs. 49.4%; 13.7 vs. 13.1%; 84.2 vs. 85.2%; 14.4 vs. 14.2%, respectively). The prevalence of obesity (32.3 vs. 37.5%, p < 0.01) and excessive waist circumference (77.5 vs. 80.7%, p < 0.01), as well as abdominal obesity (p = 43.2 vs. 46.4%, p < 0.01), were higher in rural areas in both genders. Mean levels of LDL-C (128 vs. 130 mg/dL, p = 0.04) and non-HDL-C (147 vs. 148 mg/dL, p = 0.03) were slightly higher in rural populations. Altogether, 14.3% of patients with CVD from urban areas and 11.3% from rural areas reached LDL <70 mg/dL (p = 0.04). There were no important differences in the prevalence of hypertension, diabetes, dyslipidaemia, and CVD, or in mean levels of blood pressure, cholesterol fractions, glucose, and HbA1c between Polish urban and rural primary care patient populations. A high proportion of patients in cities and an even-higher proportion in rural areas did not reach the recommended targets for blood pressure, LDL-C, and HbA1c, indicating the need for novel CVD-prevention programs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Deficiency of MicroRNA-181a results in transcriptome-wide cell-specific changes in the kidney and increases blood pressure
- Paterson, Madeleine, Jackson, Kristy, Dona, Malathi, Farrugia, Gabriella, Visniauskas, Bruna, Watson, Anna, Johnson, Chad, Prieto, Minolfa, Evans, Roger, Charchar, Fadi, Pinto, Alexander, Marques, Francine, Head, Geoffrey
- Authors: Paterson, Madeleine , Jackson, Kristy , Dona, Malathi , Farrugia, Gabriella , Visniauskas, Bruna , Watson, Anna , Johnson, Chad , Prieto, Minolfa , Evans, Roger , Charchar, Fadi , Pinto, Alexander , Marques, Francine , Head, Geoffrey
- Date: 2021
- Type: Text , Journal article
- Relation: Hypertension Vol. 78, no. 5 (Nov 2021), p. 1322-1334
- Full Text:
- Reviewed:
- Description: MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P<0.01). Compared with WT mice, renal renin was higher in the juxtaglomerular cells of KO mice. BP was similar in WT mice on a high- (3.1%) versus low- (0.3%) sodium diet (+0.4 +/- 0.8 mm Hg), but KO mice showed salt sensitivity (+3.3 +/- 0.8 mm Hg; P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA sequencing in 6699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, and Smad4. We observed upregulation of pathways related to the immune system, inflammatory response, reactive oxygen species, and nerve development, consistent with higher tyrosine hydroxylase in the kidney. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension.
- Authors: Paterson, Madeleine , Jackson, Kristy , Dona, Malathi , Farrugia, Gabriella , Visniauskas, Bruna , Watson, Anna , Johnson, Chad , Prieto, Minolfa , Evans, Roger , Charchar, Fadi , Pinto, Alexander , Marques, Francine , Head, Geoffrey
- Date: 2021
- Type: Text , Journal article
- Relation: Hypertension Vol. 78, no. 5 (Nov 2021), p. 1322-1334
- Full Text:
- Reviewed:
- Description: MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P<0.01). Compared with WT mice, renal renin was higher in the juxtaglomerular cells of KO mice. BP was similar in WT mice on a high- (3.1%) versus low- (0.3%) sodium diet (+0.4 +/- 0.8 mm Hg), but KO mice showed salt sensitivity (+3.3 +/- 0.8 mm Hg; P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA sequencing in 6699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, and Smad4. We observed upregulation of pathways related to the immune system, inflammatory response, reactive oxygen species, and nerve development, consistent with higher tyrosine hydroxylase in the kidney. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension.
Relationship between anti-DFS70 autoantibodies and oxidative stress
- Krzemień, Pawel, Kasperczyk, Slawomir, Banach, Maciej, Kasperczyk, Aleksandra, Dobrakowski, Michal, Tomasik, Tomasz, Windak, Adam, Mastej, Miroslaw, Catapano, Alberico, Ray, Kausik, Mikhailidis, Dimitri, Toth, Peter, Howard, George, Lip, Gregory, Tomaszewski, Maciej, Charchar, Fadi, Sattar, Naveed, Williams, Bryan, MacDonald, Thomas, Penson, Peter, Jóźwiak, J, Al-Shaer, B., Andrusewicz, W., Andrzejczuk-Rosa, M., Anusz-Gaszewska, E., Bagińska, A., Balawajder, P., Bańka, G., Barańska-Skubisz, E., Barbara Przyczyna, B.
- Authors: Krzemień, Pawel , Kasperczyk, Slawomir , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, J , Al-Shaer, B. , Andrusewicz, W. , Andrzejczuk-Rosa, M. , Anusz-Gaszewska, E. , Bagińska, A. , Balawajder, P. , Bańka, G. , Barańska-Skubisz, E. , Barbara Przyczyna, B.
- Date: 2022
- Type: Text , Journal article
- Relation: Biomarker Insights Vol. 17, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. © The Author(s) 2022. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Krzemień, Pawel , Kasperczyk, Slawomir , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, J , Al-Shaer, B. , Andrusewicz, W. , Andrzejczuk-Rosa, M. , Anusz-Gaszewska, E. , Bagińska, A. , Balawajder, P. , Bańka, G. , Barańska-Skubisz, E. , Barbara Przyczyna, B.
- Date: 2022
- Type: Text , Journal article
- Relation: Biomarker Insights Vol. 17, no. (2022), p.
- Full Text:
- Reviewed:
- Description: Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. © The Author(s) 2022. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics
- Xu, Xiaoguang, Eales, James, Jiang, Xiao, Sanderson, Eleanor, Drzal, Maciej, Saluja, Sushant, Scannali, David, Williams, Bryan, Morris, Andrew, Guzik, Tomasz, Charchar, Fadi, Holmes, Michael, Tomaszewski, Maciej
- Authors: Xu, Xiaoguang , Eales, James , Jiang, Xiao , Sanderson, Eleanor , Drzal, Maciej , Saluja, Sushant , Scannali, David , Williams, Bryan , Morris, Andrew , Guzik, Tomasz , Charchar, Fadi , Holmes, Michael , Tomaszewski, Maciej
- Date: 2022
- Type: Text , Journal article
- Relation: Cardiovascular research Vol. 118, no. 15 (2022), p. 3151-3161
- Full Text:
- Reviewed:
- Description: AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in
- Authors: Xu, Xiaoguang , Eales, James , Jiang, Xiao , Sanderson, Eleanor , Drzal, Maciej , Saluja, Sushant , Scannali, David , Williams, Bryan , Morris, Andrew , Guzik, Tomasz , Charchar, Fadi , Holmes, Michael , Tomaszewski, Maciej
- Date: 2022
- Type: Text , Journal article
- Relation: Cardiovascular research Vol. 118, no. 15 (2022), p. 3151-3161
- Full Text:
- Reviewed:
- Description: AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in
Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications
- Tomaszewski, Maciej, Morris, Andrew, Howson, Joanna, Franceschini, Nora, Eales, James, Xu, Xiaoguang, Dikalov, Sergey, Guzik, Tomasz, Humphreys, Benjamin, Harrap, Stephen, Charchar, Fadi
- Authors: Tomaszewski, Maciej , Morris, Andrew , Howson, Joanna , Franceschini, Nora , Eales, James , Xu, Xiaoguang , Dikalov, Sergey , Guzik, Tomasz , Humphreys, Benjamin , Harrap, Stephen , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Kidney International Vol. 102, no. 3 (2022), p. 492-505
- Full Text:
- Reviewed:
- Description: Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage. © 2022 International Society of Nephrology
- Authors: Tomaszewski, Maciej , Morris, Andrew , Howson, Joanna , Franceschini, Nora , Eales, James , Xu, Xiaoguang , Dikalov, Sergey , Guzik, Tomasz , Humphreys, Benjamin , Harrap, Stephen , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Kidney International Vol. 102, no. 3 (2022), p. 492-505
- Full Text:
- Reviewed:
- Description: Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage. © 2022 International Society of Nephrology
Renin-angiotensin system inhibitors in patients With COVID-19 : a meta-analysis of randomized controlled trials led by the International Society of Hypertension
- Gnanenthiran, Sonali, Borghi, Claudio, Burger, Dylan, Caramelli, Bruno, Charchar, Fadi, Chirinos, Julio, Cohen, Jordana, Cremer, Antoine, Di Tanna, Gian, Duvignaud, Alexandre, Freilich, Daniel, Gommans, D., Gracia-Ramos, Abraham, Murray, Thomas, Pelorosso, Facundo, Poulter, Neil, Puskarich, Michael, Rizas, Konstantinos, Rothlin, Rodolfo, Schlaich, Markus, Schreinlecher, Michael, Steckelings, Ulrike, Sharma, Abhinav, Stergiou, George, Tignanelli, Christopher, Tomaszewski, Maciej, Unger, Thomas, van Kimmenade, Roland, Wainford, Richard, Williams, Bryan, Rodgers, Anthony, Schutte, Aletta
- Authors: Gnanenthiran, Sonali , Borghi, Claudio , Burger, Dylan , Caramelli, Bruno , Charchar, Fadi , Chirinos, Julio , Cohen, Jordana , Cremer, Antoine , Di Tanna, Gian , Duvignaud, Alexandre , Freilich, Daniel , Gommans, D. , Gracia-Ramos, Abraham , Murray, Thomas , Pelorosso, Facundo , Poulter, Neil , Puskarich, Michael , Rizas, Konstantinos , Rothlin, Rodolfo , Schlaich, Markus , Schreinlecher, Michael , Steckelings, Ulrike , Sharma, Abhinav , Stergiou, George , Tignanelli, Christopher , Tomaszewski, Maciej , Unger, Thomas , van Kimmenade, Roland , Wainford, Richard , Williams, Bryan , Rodgers, Anthony , Schutte, Aletta
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of the American Heart Association Vol. 11, no. 17 (2022), p.
- Full Text:
- Reviewed:
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05– 3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. CONCLUSIONS: This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angio-tensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19. © 2022 The Authors.
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at
- Authors: Gnanenthiran, Sonali , Borghi, Claudio , Burger, Dylan , Caramelli, Bruno , Charchar, Fadi , Chirinos, Julio , Cohen, Jordana , Cremer, Antoine , Di Tanna, Gian , Duvignaud, Alexandre , Freilich, Daniel , Gommans, D. , Gracia-Ramos, Abraham , Murray, Thomas , Pelorosso, Facundo , Poulter, Neil , Puskarich, Michael , Rizas, Konstantinos , Rothlin, Rodolfo , Schlaich, Markus , Schreinlecher, Michael , Steckelings, Ulrike , Sharma, Abhinav , Stergiou, George , Tignanelli, Christopher , Tomaszewski, Maciej , Unger, Thomas , van Kimmenade, Roland , Wainford, Richard , Williams, Bryan , Rodgers, Anthony , Schutte, Aletta
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of the American Heart Association Vol. 11, no. 17 (2022), p.
- Full Text:
- Reviewed:
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05– 3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. CONCLUSIONS: This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angio-tensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19. © 2022 The Authors.
- Description: BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at
Addressing global disparities in blood pressure control : perspectives of the International Society of Hypertension
- Schutte, Aletta, Jafar, Tazeen, Poulter, Neil, Damasceno, Albertino, Khan, Nadia, Nilsson, Peter, Alsaid, Jafar, Neupane, Dinesh, Kario, Kazuomi, Beheiry, Hind, Brouwers, Sofie, Burger, Dylan, Charchar, Fadi, Cho, Myeong-Chan, Guzik, Tomasz, Haji Al-Saedi, Ghazi, Ishaq, Muhammad, Itoh, Hiroshi, Jones, Erika, Khan, Taskeen, Kokubo, Yoshihiro, Kotruchin, Praew, Muxfeldt, Elizabeth, Odili, Augustine, Patil, Mansi, Ralapanawa, Udaya, Romero, Cesar, Schlaich, Markus, Shehab, Abdulla, Mooi, Ching
- Authors: Schutte, Aletta , Jafar, Tazeen , Poulter, Neil , Damasceno, Albertino , Khan, Nadia , Nilsson, Peter , Alsaid, Jafar , Neupane, Dinesh , Kario, Kazuomi , Beheiry, Hind , Brouwers, Sofie , Burger, Dylan , Charchar, Fadi , Cho, Myeong-Chan , Guzik, Tomasz , Haji Al-Saedi, Ghazi , Ishaq, Muhammad , Itoh, Hiroshi , Jones, Erika , Khan, Taskeen , Kokubo, Yoshihiro , Kotruchin, Praew , Muxfeldt, Elizabeth , Odili, Augustine , Patil, Mansi , Ralapanawa, Udaya , Romero, Cesar , Schlaich, Markus , Shehab, Abdulla , Mooi, Ching
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cardiovascular Research Vol. 119, no. 2 (2023), p. 381-409
- Full Text:
- Reviewed:
- Description: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework. © 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Schutte, Aletta , Jafar, Tazeen , Poulter, Neil , Damasceno, Albertino , Khan, Nadia , Nilsson, Peter , Alsaid, Jafar , Neupane, Dinesh , Kario, Kazuomi , Beheiry, Hind , Brouwers, Sofie , Burger, Dylan , Charchar, Fadi , Cho, Myeong-Chan , Guzik, Tomasz , Haji Al-Saedi, Ghazi , Ishaq, Muhammad , Itoh, Hiroshi , Jones, Erika , Khan, Taskeen , Kokubo, Yoshihiro , Kotruchin, Praew , Muxfeldt, Elizabeth , Odili, Augustine , Patil, Mansi , Ralapanawa, Udaya , Romero, Cesar , Schlaich, Markus , Shehab, Abdulla , Mooi, Ching
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cardiovascular Research Vol. 119, no. 2 (2023), p. 381-409
- Full Text:
- Reviewed:
- Description: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework. © 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Fasting triglycerides are positively associated with cardiovascular mortality risk in people with diabetes
- Wang, Yutang, Fang, Yan, Magliano, Dianna, Charchar, Fadi, Sobey, Christopher, Drummond, Grant, Golledge, Jonathan
- Authors: Wang, Yutang , Fang, Yan , Magliano, Dianna , Charchar, Fadi , Sobey, Christopher , Drummond, Grant , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: Cardiovascular Research Vol. 119, no. 3 (2023), p. 826-834
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Aims We investigated the association of fasting triglycerides with cardiovascular disease (CVD) mortality. Methods and results This cohort study included US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. CVD mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglycerides for CVD mortality. The cohort included 26 570 adult participants, among which 3978 had diabetes. People with higher triglycerides had a higher prevalence of diabetes at baseline. The cohort was followed up for a mean of 12.0 years with 1492 CVD deaths recorded. A 1-natural-log-unit higher triglyceride was associated with a 30% higher multivariate-adjusted risk of CVD mortality in participants with diabetes (HR, 1.30; 95% CI, 1.08–1.56) but not in those without diabetes (HR, 0.95; 95% CI, 0.83–1.07). In participants with diabetes, people with high triglycerides (200–499 mg/dL) had a 44% (HR, 1.44; 95% CI, 1.12–1.85) higher multivariate-adjusted risk of CVD mortality compared with those with normal triglycerides (<150 mg/dL). The findings remained significant when diabetes was defined by fasting glucose levels alone, or after further adjustment for the use of lipid-lowering medications, or after the exclusion of those who took lipid-lowering medications. Conclusion This study demonstrates that fasting triglycerides of
- Authors: Wang, Yutang , Fang, Yan , Magliano, Dianna , Charchar, Fadi , Sobey, Christopher , Drummond, Grant , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: Cardiovascular Research Vol. 119, no. 3 (2023), p. 826-834
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Aims We investigated the association of fasting triglycerides with cardiovascular disease (CVD) mortality. Methods and results This cohort study included US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. CVD mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglycerides for CVD mortality. The cohort included 26 570 adult participants, among which 3978 had diabetes. People with higher triglycerides had a higher prevalence of diabetes at baseline. The cohort was followed up for a mean of 12.0 years with 1492 CVD deaths recorded. A 1-natural-log-unit higher triglyceride was associated with a 30% higher multivariate-adjusted risk of CVD mortality in participants with diabetes (HR, 1.30; 95% CI, 1.08–1.56) but not in those without diabetes (HR, 0.95; 95% CI, 0.83–1.07). In participants with diabetes, people with high triglycerides (200–499 mg/dL) had a 44% (HR, 1.44; 95% CI, 1.12–1.85) higher multivariate-adjusted risk of CVD mortality compared with those with normal triglycerides (<150 mg/dL). The findings remained significant when diabetes was defined by fasting glucose levels alone, or after further adjustment for the use of lipid-lowering medications, or after the exclusion of those who took lipid-lowering medications. Conclusion This study demonstrates that fasting triglycerides of
Serum antinuclear autoantibodies are associated with measures of oxidative stress and lifestyle factors : analysis of LIPIDOGRAM2015 and LIPIDOGEN2015 studies
- Krzemień, Pawel, Kasperczyk, S, Banach, Maciej, Kasperczyk, Aleksandra, Dobrakowski, Michal, Tomasik, Tomasz, Windak, Adam, Mastej, Miroslaw, Catapano, Alberico, Ray, Kausik, Mikhailidis, Dimitri, Toth, Peter, Howard, George, Lip, Gregory, Tomaszewski, Maciej, Charchar, Fadi, Sattar, Naveed, Williams, Bryan, MacDonald, Thomas, Penson, Peter, Jóźwiak, Jacek
- Authors: Krzemień, Pawel , Kasperczyk, S , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, Jacek
- Date: 2023
- Type: Text , Journal article
- Relation: Archives of Medical Science Vol. 19, no. 5 (2023), p. 1214-1227
- Full Text:
- Reviewed:
- Description: Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as “neo-antigens” and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner. © 2021 Termedia & Banach.
- Authors: Krzemień, Pawel , Kasperczyk, S , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, Jacek
- Date: 2023
- Type: Text , Journal article
- Relation: Archives of Medical Science Vol. 19, no. 5 (2023), p. 1214-1227
- Full Text:
- Reviewed:
- Description: Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as “neo-antigens” and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner. © 2021 Termedia & Banach.