Showing items 1 - 20 of 124

Adjustment for body mass index changes inverse associations of HDL-cholesterol with blood pressure and hypertension to positive associations

- Yang, Guang, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Christopher, Witting, Paul, Denton, Kate, Charchar, Fadi, Golledge, Jonathan, Wang, Yutang

  • Authors: Yang, Guang , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Christopher , Witting, Paul , Denton, Kate , Charchar, Fadi , Golledge, Jonathan , Wang, Yutang
  • Date: 2022
  • Type: Text , Journal article
  • Relation: Journal of Human Hypertension Vol. 36, no. 6 (2022), p. 570-579
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  • Description: The associations between high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) or hypertension are inconsistent in previous studies. This study aimed to assess these associations in a large cohort of Chinese adults and across different age groups. This cross-sectional association study included 22,081 Chinese adults. Associations of HDL-C with BP and hypertension were analyzed using linear or logistic regression, with or without adjustment for confounding factors. HDL-C was inversely associated with BP and hypertension. These associations were still apparent after adjustment for age, sex, fasting plasma glucose, and low-density lipoprotein cholesterol. Sub-analyses revealed: (1) in the whole cohort and females alone, HDL-C was inversely associated with BP and hypertension in young and middle-aged but not older participants; (2) in males alone, HDL-C was not associated with systolic BP or hypertension. However, HDL-C was either inversely, or not, or positively associated with BP in young, middle-aged, and older males, respectively. After further adjustment for body mass index (BMI), the negative associations of HDL-C with BP and hypertension in the whole cohort became positive ones, and the positive associations only presented in males. These findings suggest that further adjustment for BMI changes inverse associations of HDL-cholesterol with BP and hypertension to positive associations in a cohort of Chinese adults. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population : a nationwide observational, cross-sectional study

- Krzemie, Kasperczyk, Sławomir, Banach, Maciejc, Kasperczyk, Aleksandra, Dobrakowski, Michał, Tomasik, Tomasz, Windak, Adam, Mastej, Mirosław, Catapano, Alberico, Ray, Kausik, Mikhailidis, Dimitri, Toth, Peter, Howard, George, Lip, Gregory, Tomaszewski, Macie, Charchar, Fadi, Sattar, Naveed, Williams, Bryan, MacDonald, Thomas, Penson, Peter, J, Al-Shaer B, Andrusewicz W., Anusz-Gaszewska E., B, Balawajder P., Bańka G., Barańska-Skubisz E., Przyczyna, B., Bartkowiak S.

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

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
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  • 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

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.
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  • 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**

Telomere therapy for chronic kidney disease

- Akinnibosun, Olutope, Maier, Michelle, Eales, James, Tomaszewski, Maciej, Charchar, Fadi

  • Authors: Akinnibosun, Olutope , Maier, Michelle , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
  • Date: 2022
  • Type: Text , Journal article
  • Relation: Epigenomics Vol. 14, no. 17 (2022), p. 1039-1054
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  • Description: Chronic kidney disease (CKD) is estimated to affect almost 10% of individuals worldwide and is one of the leading causes of morbidity and mortality. Renal fibrosis, a central pathway in CKD progression (irrespective of etiology), is associated with shortened or dysfunctional telomeres in animal studies. Telomeres are specialized nucleoprotein structures located at the chromosome end that maintain genomic integrity. The mechanisms of associations between telomere length and CKD have not yet been fully elucidated, however, CKD patients with shorter telomere length may have decreased renal function and a higher mortality rate. A plethora of ongoing research has focused on possible therapeutic applications of telomeres with the overall goal to preserve telomere length as a therapy to treat CKD. Chronic kidney disease or CKD is one of the leading causes of illness and death worldwide. Scarring of the kidney tissue that occurs in CKD has been associated with shorter telomeres in studies using rats. Telomeres, said to act as the cellular ‘shoelace caps’, maintain the structure of chromosomes, allowing for genetic material inside cells to divide correctly. The length of telomeres (TL) is influenced by diverse factors such as genetics and lifestyle. The underlying processes for the associations between TL and CKD are still not understood, however, patients with CKD and shorter TL have reduced kidney function and an increased death rate. Therefore, research is focused on possible ways to preserve TL and treat CKD. Preserving telomere length may reduce rates of chronic kidney disease, thereby decreasing morbidity & mortality worldwide.

A modified MTS proliferation assay for suspended cells to avoid the interference by hydralazine and β-Mercaptoethanol

- Wang, Yutang, Nguyen, Dinh, Anesi, Jack, Kelly, Jason, Ahmady, Fahima, Charchar, Fadi

  • Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Kelly, Jason , Ahmady, Fahima , Charchar, Fadi
  • Date: 2021
  • Type: Text , Journal article
  • Relation: Assay and Drug Development Technologies Vol. 19, no. 3 (2021), p. 184-190. https://purl.org/au-research/grants/nhmrc/1062671
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  • Description: The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay is one of the most commonly used tests of cell proliferation. Hydralazine has been reported to interfere with the performance of the MTS assay when used on adherent cells. This study aimed to investigate whether hydralazine interferes with the performance of the MTS assay on suspended cells. THP-1 (a monocytic leukemia cell line) cells were cultured in the presence or absence of hydralazine (0, 10, 50, 100, and 500 μM) for 2 or 24 h. Cell numbers were analyzed using the MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established by centrifuging the cells and replacing the test medium with fresh culture medium immediately before the addition of the MTS reagent. Culture of THP-1 cells with hydralazine at concentrations of 50, 100, and 500 μM for 2 h increased absorbance (p < 0.001) in the standard MTS assay, whereas both the trypan blue exclusion assay and microscopy suggested no change in cell numbers. Culture of THP-1 cells with 100 and 500 μm 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 (100 and 500 μM) increased absorbance in a time- and concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy using THP-1 cells. In addition, the modified MTS assay produced reliable results when K562 and Jurkat cells were incubated with hydralazine or β-mercaptoethanol (βME). In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and βME when assessing suspended cells. © Copyright 2021, Mary Ann Liebert, Inc., publishers 2021. *Please note that there are multiple authors for this article therefore only the name of the Federation University Australia affiliates “Yutang Wang, Dinh Nguyen, Jack Anesi, Jason Kelly, Fahima Ahmady, 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
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  • 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.

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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  • 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.

Establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys

- Wang, Yutang, Charchar, Fadi

  • Authors: Wang, Yutang , Charchar, Fadi
  • Date: 2021
  • Type: Text , Journal article
  • Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
  • Relation: https://purl.org/au-research/grants/nhmrc/1062671
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  • Description: Men have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9472 participants (weighted sample size of 184,342,210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys. © 2021, The Author(s).

Exercise, epigenetics, and aging

- Chilton, Warrick, Maier, Maier, Akinnibosun, Olutope, O’Brien, Brendan, Charchar, Fadi

Hyperuricemia is independently associated with hypertension in men under 60 years in a general Chinese population

- Qian, Tingting, Sun, Hui, Xu, Qun, Charchar, Fadi, Wang, Yutang

  • Authors: Qian, Tingting , Sun, Hui , Xu, Qun , Charchar, Fadi , Wang, Yutang
  • Date: 2021
  • Type: Text , Journal article
  • Relation: Journal of Human Hypertension Vol. 35, no. 11 (2021), p. 1020-1028
  • Relation: https://purl.org/au-research/grants/nhmrc/1062671
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  • Description: Hyperuricemia has been associated with hypertension, however, whether this association exists across all decades of adult life is unknown. This study aimed to assess the association between hyperuricemia and hypertension in relation to age. This retrospective cross-sectional study included a total of 22,556 adult Chinese people who attended Health Physical Examination in a Chinese hospital. Participants were aged between 18 and 95 years (mean [standard deviation], 45.4 [14.0]). Serum uric acid levels and blood pressure were measured. Associations between serum uric acid and blood pressure, and between hyperuricemia and hypertension diagnosis were analyzed using linear or logistic regression, adjusting for confounding risk factors including age, sex, total cholesterol, high-density lipoprotein cholesterol, and fasting blood glucose. Sub-analysis was stratified by age and sex. Before adjustment, high serum uric acid was associated with higher systolic blood pressure (β = 0.214, P < 0.001) and higher diastolic blood pressure (β = 0.271, P < 0.001). Hyperuricemia was associated with hypertension diagnosis (OR, 1.763; 95% CI, 1.635–1.901; P < 0.001) in an unadjusted analysis. These findings remained significant after adjusting for confounding factors. Sub-analysis suggested that the association between uric acid and blood pressure was weaker in older age groups and the association between hyperuricemia and hypertension was limited to people under 60 years. Hyperuricemia was independently associated with hypertension diagnosis in men but not in women, and the independent association between hyperuricemia and hypertension only presented in men under 60 years. This study suggests that hyperuricemia is independently associated with hypertension in Chinese men under 60 years. © 2020, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature. **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 and Yutang Wang” is provided in this record**

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
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  • 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.

Plasma lipocalin-2/NGAL is stable over 12 weeks and is not modulated by exercise or dieting

- Nakai, Michael, Prestes, Priscilla, O’Brien, Brendan, Charchar, Fadi, Marques, Francine

  • Authors: Nakai, Michael , Prestes, Priscilla , O’Brien, Brendan , Charchar, Fadi , Marques, Francine
  • Date: 2021
  • Type: Text , Journal article
  • Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
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  • Description: Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18–55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise. © 2021, The Author(s). *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Priscilla Prestes, Brendan O'Brien, Fadi Charchar and Francine Marques” is provided in this record** .

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

Reduced renal function may explain the higher prevalence of hyperuricemia in older people

- Wang, Yutang, Zhang, Wanlin, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Chris, Charchar, Fadi, Golledge, Jonathan, Yang, Guang

  • Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
  • Date: 2021
  • Type: Text , Journal article
  • Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
  • Relation: https://purl.org/au-research/grants/nhmrc/1062671
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  • Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).

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**

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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  • 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**

Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney

- Eales, James, Jiang, Xiao, Xu, Xiaoguang, Prestes, Priscilla, Charchar, Fadi

  • Authors: Eales, James , Jiang, Xiao , Xu, Xiaoguang , Prestes, Priscilla , Charchar, Fadi
  • Date: 2021
  • Type: Text , Journal article
  • Relation: Nature Genetics Vol. 53, no. 5 (2021), p. 630-637
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  • Description: The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension. © 2021, Crown.

2020 International Society of Hypertension global hypertension practice guidelines

- Unger, Thomas, Borghi, Claudio, Charchar, Fadi, Khan, Nadia, Poulter, Neil