- Tomaszewski, Maciej, Charchar, Fadi, Barnes, Timothy, Maric, Christine, Samani, Nilesh, Zukowska-Szczechowska, Ewa
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Maric, Christine , Samani, Nilesh , Zukowska-Szczechowska, Ewa
- Date: 2009
- Type: Text , Conference paper
- Relation: , p. S148
- Full Text: false
- Tomaszewski, Maciej, Charchar, Fadi, Maric, Christine, Kuzniewicz, Roman, Gola, Mateusz, Grzeszczak, Wladyslaw, Samani, Nilesh, Zukowska-Szczechowska, Ewa
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Maric, Christine , Kuzniewicz, Roman , Gola, Mateusz , Grzeszczak, Wladyslaw , Samani, Nilesh , Zukowska-Szczechowska, Ewa
- Date: 2009
- Type: Text , Journal article
- Relation: American Journal of Hypertension Vol. 22, no. 1 (2009), p. 100-105
- Full Text: false
- Reviewed:
- Description: Background: Men exhibit higher risk of nondiabetic renal diseases than women. This male susceptibility to renal disease may be mediated by gender-specific factors such as sex hormones. Methods: We have undertaken a cross-sectional examination of associations between renal function (creatinine clearance estimated based on Cockcroft-Gault equation) and circulating levels of sex steroids (total testosterone, total estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and dihydrotestosterone) in 928 young (mean age: 18.5 ± 1.2 years) men. Results: Both androstenedione and DHEA-S showed inverse linear associations with renal function in the crude analysis of lean men (those with body mass index (BMI) less than median). However, only DHEA-S retained its association with renal function in lean subjects after adjustment - assuming no changes in other independent variables 1 s.d. increase in DHEA-S was associated with 13%-s.d. decrease in creatinine clearance (P = 0.004). Testosterone decreased across tertiles of creatinine clearance only in the crude analysis of nonlean (BMI greater than median) subjects (P < 0.001). The adjusted regression analysis that assumed no changes in other independent variables showed that 1 s.d. increase in total testosterone was associated with 11%-s.d. decrease in creatinine clearance of nonlean men (P = 0.006). Factor analysis confirmed an inverse association of renal function with both sex steroids and a different pattern of their loadings on glomerular filtration-related factors in lean (DHEA-S) and nonlean (testosterone) subjects. Conclusions: Our data may suggest that androgens are inversely associated with estimated renal function in apparently healthy men without history of cardiovascular disease. © 2009 American Journal of Hypertension, Ltd.
- Description: C1
Pathway analysis shows association between FGFBP1 and hypertension
- Tomaszewski, Maciej, Charchar, Fadi, Nelson, Christopher, Barnes, Timothy, Denniff, Matthew, Kaiser, Michael, Debiec, Radoslaw, Christofidou, Paraskevi, Rafelt, Suzanne, Van Harst, Pim Der, Wang, William, Maric, Christine, Zukowska-Szczechowska, Ewa, Samani, Nilesh
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Nelson, Christopher , Barnes, Timothy , Denniff, Matthew , Kaiser, Michael , Debiec, Radoslaw , Christofidou, Paraskevi , Rafelt, Suzanne , Van Harst, Pim Der , Wang, William , Maric, Christine , Zukowska-Szczechowska, Ewa , Samani, Nilesh
- Date: 2011
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 22, no. 5 (2011), p. 947-955
- Full Text: false
- Reviewed:
- Description: Variants in the gene encoding fibroblast growth factor 1 (FGF1) co-segregate with familial susceptibility to hypertension, and glomerular upregulation of FGF1 associates with hypertension. To investigate whether variants in other members of the FGF signaling pathway may also associate with hypertension, we genotyped 629 subjects from 207 Polish families with hypertension for 79 single nucleotide polymorphisms in eight genes of this network. Family-based analysis showed that parents transmitted the major allele of the rs16892645 polymorphism in the gene encoding FGF binding protein 1 (FGFBP1) to hypertensive offspring more frequently than expected by chance (P = 0.005). An independent cohort of 807 unrelated Polish subjects validated this association. Furthermore, compared with normotensive subjects, hypertensive subjects had approximately 1.5- and 1.4-fold higher expression of renal FGFBP1 mRNA and protein (P = 0.04 and P = 0.001), respectively. By immunohistochemistry, hypertensionrelated upregulation of FGFBP1 was most apparent in the glomerulus and juxtaglomerular space. Taken together, these data suggest that FGFBP1 associates with hypertension and that systematic analysis of signaling pathways can identify previously undescribed genetic associations. Copyright © 2011 by the American Society of Nephrology.
- Tomaszewski, Maciej, Charchar, Fadi, Barnes, Timothy, Maric, Christine, Zukowska-Szczechowska, Ewa, Samani, Nilesh
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Maric, Christine , Zukowska-Szczechowska, Ewa , Samani, Nilesh
- Date: 2010
- Type: Text , Conference paper
- Relation: Paper presented at British Cardiovascular Society Annual Conference 2010, Manchester Central, Manchester, UK : 7th-9th June 2010
- Full Text: false
- Description: Essential hypertension is a complex, multifactorial disease with a strong genetic component. Fibroblast growth factor 1 gene (FGF1) is one of the most relevant candidates having been associated not only with familial susceptibility to hypertension but also with up-regulation within the glomerulus of the human hypertensive kidney/Circulation 2007;116:1915e24/. We have hypothesised that systematic analysis of genes interacting with FGF1 may uncover novel variants underlying essential hypertension. Seventy-nine common (minor allele frequency$0.1) tagging (r2$0.8) and functional single nucleotide polymorphisms (SNPs) spanning eight critical components of the FGF (fibroblast growth factor) pathway (FGF2, FGFR1, FGFR2, FGFR3, FGFR4, FGFBP1, FIBP, SPRY1) were genotyped by MALDI-TOF mass spectrometry in 629 subjects from 207 Polish hypertensive families (Silesian Hypertension Study d SHS). 83.5% of genotyped SNPs that passed quality control filters provided 92.9% genetic coverage of FGF pathway loci. Family-based analysis in SHS revealed that alleles of three SNPs (rs2956724, rs2245964 and rs16892645) in two loci (FGFR1 and FGFBP1) were transmitted to hypertensive offspring more frequently than expected by chance. However, only one association survived correction for multiple testing e major allele of rs16892645 in FGFBP1 was over-transmitted from heterozygous parents to hypertensive offspring more frequently than expected by chance (p¼0.0048, false discovery rate<0.25). The association between rs16892645 and hypertension was replicated in an independent cohort of 807 Polish subjects from Silesian Cardiovascular Study d each major allele copy of rs16892645 increased the odds of hypertension approximately by 1.5 (odds ratio: 1.5; 95% CI: 1.1 to to 2.2, p¼0.04). Association between FGFBP1 and hypertension was also apparent at the protein expression level d compared with normotensive patients, hypertensives from Silesian Renal Tissue Bank showed approximately 1.4-fold higher renal abundance of FGFBP1 in Western blotting (p¼0.001). Immunohistochemical analysis revealed that hypertension-related up-regulation of FGFBP1 was exclusive to renal glomeruli. These data show that FGFBP1da gene that encodes a carrier protein for FGF1 d is associated with human hypertension. We also reveal that up-regulation of FGFBP1 maps to the same histological compartment where FGF1 was shown to be most abundant (renal glomeruli). Our study also proves that systematic genetic analysis of signalling pathways is a strategy with a potential to identify novel molecular mechanisms underlying blood pressure elevation.
Association between lipid profile and circulating concentrations of estrogens in young men
- Tomaszewski, Maciej, Maric, Christine, Zuzniewicz, Roman, Gola, Mateusz, Grzeszczak, Wladyslaw, Samani, Nilesh, Zukowska-Szczechowska, Ewa, Charchar, Fadi
- Authors: Tomaszewski, Maciej , Maric, Christine , Zuzniewicz, Roman , Gola, Mateusz , Grzeszczak, Wladyslaw , Samani, Nilesh , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2009
- Type: Text , Journal article
- Relation: Atheroclerosis Vol. 203, no. (2009), p. 257-262
- Full Text: false
- Reviewed:
- Description: Objectives: Men show higher rates of cardiovascular morbidity and mortality than pre-menopausal women and this sexual dimorphism may be related to sex-specific effects of sex steroids on cardiovascular risk factors. Unlike androgens, estrogens were not extensively investigated in relation to cardiovascular phenotypes in men.
- Description: C1
Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure
- Tomaszewski, Maciej, Eales, James, Denniff, Matthew, Myers, Stephen, Chew, Guatsiew, Nelson, Christopher, Christofidou, Paraskevi, Desai, Aishwarya, Büsst, Cara, Wojnar, Lukasz, Musialik, Katarzyna, Jozwiak, Jacek, Debiec, Radoslaw, Dominiczak, Anna, Navis, Gerjan, van Gilst, Wiek, van der Harst, Pim, Samani, Nilesh, Harrap, Stephen, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Charchar, Fadi
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
Measurement of absolute copy number variation reveals association with essential hypertension
- Marques, Francine, Prestes, Priscilla, Pinheiro, Leonardo, Scurrah, Katrina, Emslie, Kerry, Tomaszewski, Maciej, Harrap, Stephen, Charchar, Fadi
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
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.
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
May measurement month 2018 : A pragmatic global screening campaign to raise awareness of blood pressure by the international society of hypertension
- Beaney, Thomas, Burrell, Louise, Castillo, Rafael, Charchar, Fadi, Cro, Suzie, Damasceno, Albertino, Kruger, Ruan, Nilsson, Peter, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Schutte, Aletta, Tomaszewski, Maciej, Touyz, Rhian, Wang, Ji-Guang, Weber, Michael, Poulter, Neil
- Authors: Beaney, Thomas , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Cro, Suzie , Damasceno, Albertino , Kruger, Ruan , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Schutte, Aletta , Tomaszewski, Maciej , Touyz, Rhian , Wang, Ji-Guang , Weber, Michael , Poulter, Neil
- Date: 2019
- Type: Text , Journal article , Review
- Relation: European Heart Journal Vol. 40, no. 25 (2019), p. 2006-2017
- Full Text:
- Reviewed:
- Description: Aims: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
- Authors: Beaney, Thomas , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Cro, Suzie , Damasceno, Albertino , Kruger, Ruan , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Schutte, Aletta , Tomaszewski, Maciej , Touyz, Rhian , Wang, Ji-Guang , Weber, Michael , Poulter, Neil
- Date: 2019
- Type: Text , Journal article , Review
- Relation: European Heart Journal Vol. 40, no. 25 (2019), p. 2006-2017
- Full Text:
- Reviewed:
- Description: Aims: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
The y chromosome : A blueprint for men's health?
- Maan, Akhlaq, Eales, James, Akbarov, Artur, Rowland, Joshua, Xu, Xiaoguang, Jobling, Mark, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Maan, Akhlaq , Eales, James , Akbarov, Artur , Rowland, Joshua , Xu, Xiaoguang , Jobling, Mark , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2017
- Type: Text , Journal article , Review
- Relation: European Journal of Human Genetics Vol. 25, no. 11 (2017), p. 1181-1188
- Full Text:
- Reviewed:
- Description: The Y chromosome has long been considered a genetic wasteland' on a trajectory to completely disappear from the human genome. The perception of its physiological function was restricted to sex determination and spermatogenesis. These views have been challenged in recent times with the identification of multiple ubiquitously expressed Y-chromosome genes and the discovery of several unexpected associations between the Y chromosome, immune system and complex polygenic traits. The collected evidence suggests that the Y chromosome influences immune and inflammatory responses in men, translating into genetically programmed susceptibility to diseases with a strong immune component. Phylogenetic studies reveal that carriers of a common European lineage of the Y chromosome (haplogroup I) possess increased risk of coronary artery disease. This occurs amidst upregulation of inflammation and suppression of adaptive immunity in this Y lineage, as well as inferior outcomes in human immunodeficiency virus infection. From structural analysis and experimental data, the UTY (Ubiquitously Transcribed Tetratricopeptide Repeat Containing, Y-Linked) gene is emerging as a promising candidate underlying the associations between Y-chromosome variants and the immunity-driven susceptibility to complex disease. This review synthesises the recent structural, experimental and clinical insights into the human Y chromosome in the context of men's susceptibility to disease (with a particular emphasis on cardiovascular disease) and provides an overview of the paradigm shift in the perception of the Y chromosome. © 2017 The Author(s).
- Authors: Maan, Akhlaq , Eales, James , Akbarov, Artur , Rowland, Joshua , Xu, Xiaoguang , Jobling, Mark , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2017
- Type: Text , Journal article , Review
- Relation: European Journal of Human Genetics Vol. 25, no. 11 (2017), p. 1181-1188
- Full Text:
- Reviewed:
- Description: The Y chromosome has long been considered a genetic wasteland' on a trajectory to completely disappear from the human genome. The perception of its physiological function was restricted to sex determination and spermatogenesis. These views have been challenged in recent times with the identification of multiple ubiquitously expressed Y-chromosome genes and the discovery of several unexpected associations between the Y chromosome, immune system and complex polygenic traits. The collected evidence suggests that the Y chromosome influences immune and inflammatory responses in men, translating into genetically programmed susceptibility to diseases with a strong immune component. Phylogenetic studies reveal that carriers of a common European lineage of the Y chromosome (haplogroup I) possess increased risk of coronary artery disease. This occurs amidst upregulation of inflammation and suppression of adaptive immunity in this Y lineage, as well as inferior outcomes in human immunodeficiency virus infection. From structural analysis and experimental data, the UTY (Ubiquitously Transcribed Tetratricopeptide Repeat Containing, Y-Linked) gene is emerging as a promising candidate underlying the associations between Y-chromosome variants and the immunity-driven susceptibility to complex disease. This review synthesises the recent structural, experimental and clinical insights into the human Y chromosome in the context of men's susceptibility to disease (with a particular emphasis on cardiovascular disease) and provides an overview of the paradigm shift in the perception of the Y chromosome. © 2017 The Author(s).
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
Urotensin-II system in genetic control of blood pressure and renal function
- Debiec, Radoslaw, Christofidou, Paraskevi, Denniff, Matthew, Bloomer, Lisa, Bogdanski, Pawel, Wojnar, Lukasz, Musialik, Katarzyna, Charchar, Fadi, Thompson, John, Waterworth, Dawn, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Zukowska-Szczechowska, Ewa, Samani, Nilesh, Lambert, David, Tomaszewski, Maciej
- Authors: Debiec, Radoslaw , Christofidou, Paraskevi , Denniff, Matthew , Bloomer, Lisa , Bogdanski, Pawel , Wojnar, Lukasz , Musialik, Katarzyna , Charchar, Fadi , Thompson, John , Waterworth, Dawn , Song, Kijoung , Vollenweider, Peter , Waeber, Gerard , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Lambert, David , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 12 (2013), p.
- Full Text:
- Reviewed:
- Description: Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed familybased analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p< 0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates. © 2013 Debiec et al.
- Authors: Debiec, Radoslaw , Christofidou, Paraskevi , Denniff, Matthew , Bloomer, Lisa , Bogdanski, Pawel , Wojnar, Lukasz , Musialik, Katarzyna , Charchar, Fadi , Thompson, John , Waterworth, Dawn , Song, Kijoung , Vollenweider, Peter , Waeber, Gerard , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Lambert, David , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 12 (2013), p.
- Full Text:
- Reviewed:
- Description: Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed familybased analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p< 0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates. © 2013 Debiec et al.
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**
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).
A novel Y-specific long non-coding RNA associated with cellular lipid accumulation in HepG2 cells and Atherosclerosis-related genes
- Molina, Elsa, Chew, Guat, Myers, Stephen, Clarence, Elyse, Eales, James, Tomaszewski, Maciej, Charchar, Fadi
- Authors: Molina, Elsa , Chew, Guat , Myers, Stephen , Clarence, Elyse , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. 1 (2017), p. 1-12
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.
- Authors: Molina, Elsa , Chew, Guat , Myers, Stephen , Clarence, Elyse , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. 1 (2017), p. 1-12
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.
Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics
- Rowland, Joshua, Akbarov, Artur, Eales, James, Xu, Xiaoguang, Dormer, John, Guo, Hui, Denniff, Matthew, Jiang, Xiao, Ranjzad, Parisa, Nazgiewicz, Alicja, Prestes, Priscilla, Antczak, Andrzej, Szulinska, Monika, Wise, Ingrid, Zukowska-Szczechowska, Ewa, Bogdanski, Pawel, Woolf, Adrian, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Rowland, Joshua , Akbarov, Artur , Eales, James , Xu, Xiaoguang , Dormer, John , Guo, Hui , Denniff, Matthew , Jiang, Xiao , Ranjzad, Parisa , Nazgiewicz, Alicja , Prestes, Priscilla , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Zukowska-Szczechowska, Ewa , Bogdanski, Pawel , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Kidney International Vol. 95, no. 3 (2019), p. 624-635
- Full Text:
- Reviewed:
- Description: Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype–Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.
- Authors: Rowland, Joshua , Akbarov, Artur , Eales, James , Xu, Xiaoguang , Dormer, John , Guo, Hui , Denniff, Matthew , Jiang, Xiao , Ranjzad, Parisa , Nazgiewicz, Alicja , Prestes, Priscilla , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Zukowska-Szczechowska, Ewa , Bogdanski, Pawel , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Kidney International Vol. 95, no. 3 (2019), p. 624-635
- Full Text:
- Reviewed:
- Description: Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype–Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.
Longer leukocyte telomeres are associated with ultra-endurance exercise independent of cardiovascular risk factors
- Denham, Joshua, Nelson, Christopher, O'Brien, Brendan, Nankervis, Scott, Denniff, Matthew, Harvey, Jack, Marques, Francine, Codd, Veryan, Zukowska-Szczechowska, Ewa, Samani, Nilesh, Tomaszewski, Maciej, Charchar, Fadi
- Authors: Denham, Joshua , Nelson, Christopher , O'Brien, Brendan , Nankervis, Scott , Denniff, Matthew , Harvey, Jack , Marques, Francine , Codd, Veryan , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 7 (2013), p.
- Full Text:
- Reviewed:
- Description: Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners' and 56 apparently healthy males' leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41;
- Description: 2003011219
- Authors: Denham, Joshua , Nelson, Christopher , O'Brien, Brendan , Nankervis, Scott , Denniff, Matthew , Harvey, Jack , Marques, Francine , Codd, Veryan , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE Vol. 8, no. 7 (2013), p.
- Full Text:
- Reviewed:
- Description: Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners' and 56 apparently healthy males' leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41;
- Description: 2003011219
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.
Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies
- Morris, Andrew, Le, Thu, Wu, Haojia, Akbarov, Artur, van der Most, Peter, Hemani, Gibran, Smith, George, Mahajan, Anubha, Gaulton, Kyle, Nadkarni, Girish, Valladares-Salgado, Adan, Wacher-Rodarte, Niels, Mychaleckyj, Josyf, Dueker, Nicole, Guo, Xiuqing, Hai, Yang, Haessler, Jeffrey, Kamatani, Yoichiro, Stilp, Adrienne, Zhu, Gu, Cook, James, Arnlov, Johan, Blanton, Susan, de Borst, Martin, Bottinger, Erwin, Buchanan, Thomas, Cechova, Sylvia, Charchar, Fadi, Chu, Pei-Lun, Damman, Jeffrey, Eales, James, Gharavi, Ali, Giedraitis, Vilmantas, Heath, Andrew, Ipp, Eli, Kiryluk, Krzysztof, Kramer, Holly, Kubo, Michiaki, Larsson, Anders, Lindgren, Cecilia, Lu, Yingchang, Madden, Pamela, Montgomery, Grant, Papanicolaou, George, Raffel, Leslie, Sacco, Ralph, Sanchez, Elena, Stark, Holger, Sundstrom, Johan, Taylor, Kent, Xiang, Anny, Zivkovic, Aleksandra, Lind, Lars, Ingelsson, Erik, Martin, Nicholas, Whitfield, John, Cai, Jianwen, Laurie, Cathy, Okada, Yukinori, Matsuda, Koichi, Kooperberg, Charles, Chen, Yii-Der, Rundek, Tatjana, Rich, Stephen, Loos, Ruth, Parra, Esteban, Cruz, Miguel, Rotter, Jerome, Snieder, Harold, Tomaszewski, Maciej, Humphreys, Benjamin, Franceschini, Nora
- Authors: Morris, Andrew , Le, Thu , Wu, Haojia , Akbarov, Artur , van der Most, Peter , Hemani, Gibran , Smith, George , Mahajan, Anubha , Gaulton, Kyle , Nadkarni, Girish , Valladares-Salgado, Adan , Wacher-Rodarte, Niels , Mychaleckyj, Josyf , Dueker, Nicole , Guo, Xiuqing , Hai, Yang , Haessler, Jeffrey , Kamatani, Yoichiro , Stilp, Adrienne , Zhu, Gu , Cook, James , Arnlov, Johan , Blanton, Susan , de Borst, Martin , Bottinger, Erwin , Buchanan, Thomas , Cechova, Sylvia , Charchar, Fadi , Chu, Pei-Lun , Damman, Jeffrey , Eales, James , Gharavi, Ali , Giedraitis, Vilmantas , Heath, Andrew , Ipp, Eli , Kiryluk, Krzysztof , Kramer, Holly , Kubo, Michiaki , Larsson, Anders , Lindgren, Cecilia , Lu, Yingchang , Madden, Pamela , Montgomery, Grant , Papanicolaou, George , Raffel, Leslie , Sacco, Ralph , Sanchez, Elena , Stark, Holger , Sundstrom, Johan , Taylor, Kent , Xiang, Anny , Zivkovic, Aleksandra , Lind, Lars , Ingelsson, Erik , Martin, Nicholas , Whitfield, John , Cai, Jianwen , Laurie, Cathy , Okada, Yukinori , Matsuda, Koichi , Kooperberg, Charles , Chen, Yii-Der , Rundek, Tatjana , Rich, Stephen , Loos, Ruth , Parra, Esteban , Cruz, Miguel , Rotter, Jerome , Snieder, Harold , Tomaszewski, Maciej , Humphreys, Benjamin , Franceschini, Nora
- Date: 2019
- Type: Text , Journal article
- Relation: Nature Communications Vol. 10, no. 1 (2019), p. 1-14
- Full Text:
- Reviewed:
- Description: Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.
- Authors: Morris, Andrew , Le, Thu , Wu, Haojia , Akbarov, Artur , van der Most, Peter , Hemani, Gibran , Smith, George , Mahajan, Anubha , Gaulton, Kyle , Nadkarni, Girish , Valladares-Salgado, Adan , Wacher-Rodarte, Niels , Mychaleckyj, Josyf , Dueker, Nicole , Guo, Xiuqing , Hai, Yang , Haessler, Jeffrey , Kamatani, Yoichiro , Stilp, Adrienne , Zhu, Gu , Cook, James , Arnlov, Johan , Blanton, Susan , de Borst, Martin , Bottinger, Erwin , Buchanan, Thomas , Cechova, Sylvia , Charchar, Fadi , Chu, Pei-Lun , Damman, Jeffrey , Eales, James , Gharavi, Ali , Giedraitis, Vilmantas , Heath, Andrew , Ipp, Eli , Kiryluk, Krzysztof , Kramer, Holly , Kubo, Michiaki , Larsson, Anders , Lindgren, Cecilia , Lu, Yingchang , Madden, Pamela , Montgomery, Grant , Papanicolaou, George , Raffel, Leslie , Sacco, Ralph , Sanchez, Elena , Stark, Holger , Sundstrom, Johan , Taylor, Kent , Xiang, Anny , Zivkovic, Aleksandra , Lind, Lars , Ingelsson, Erik , Martin, Nicholas , Whitfield, John , Cai, Jianwen , Laurie, Cathy , Okada, Yukinori , Matsuda, Koichi , Kooperberg, Charles , Chen, Yii-Der , Rundek, Tatjana , Rich, Stephen , Loos, Ruth , Parra, Esteban , Cruz, Miguel , Rotter, Jerome , Snieder, Harold , Tomaszewski, Maciej , Humphreys, Benjamin , Franceschini, Nora
- Date: 2019
- Type: Text , Journal article
- Relation: Nature Communications Vol. 10, no. 1 (2019), p. 1-14
- Full Text:
- Reviewed:
- Description: Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.