Background: The epigenetic regulation of the renin-angiotensin-aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). Here we report the first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR).
Methods: Epigenome-wide DNA methylation was measured using the Illumina 450K array on whole blood samples of 68 Ghanaians. Differentially methylated positions (DMPs) were assessed for plasma renin concentration, aldosterone, and ARR using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes and associated these with renin and aldosterone concentration.
Results: We identified one DMP for renin, ten DMPs for aldosterone, and one DMP associated with ARR. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes were also associated with renin, aldosterone, and ARR.
Conclusion: In this first EWAS on RAAS hormones, we identified DMPs associated with renin, aldosterone, and ARR in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general and in a SSA population specifically. Replication and translational studies are needed to establish the role of these DMPs in the hypertension burden in SSA populations.
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http://dx.doi.org/10.1186/s13148-022-01378-5 | DOI Listing |
Front Vet Sci
December 2024
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Introduction: Renin-angiotensin-aldosterone system inhibition (RAASi) reduces intraglomerular pressure and is a standard therapy for dogs with proteinuric chronic kidney disease (CKD). RAASi can acutely decrease glomerular filtration rate (GFR); however, its effects on the marker of GFR serum symmetric dimethylarginine (SDMA) concentration in dogs have not been specifically evaluated. The objective of this study was to evaluate changes, relative to pretreatment values, in serum SDMA concentrations in dogs with proteinuric CKD receiving RAASi therapy.
View Article and Find Full Text PDFBr J Anaesth
December 2024
Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address:
Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.
Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).
Clin Nutr
December 2024
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States of America; Department of Medicine, Boston VA Healthcare System, Boston, MA 02130, United States of America.
Background & Aims: Renin-independent aldosteronism (RIA) refers to a spectrum of autonomous aldosterone hypersecretion. We aimed to explore the genetical relationship between RIA and metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis.
Methods: We included 125357 participants from the cohort of United Kingdom Biobank.
Clin Exp Med
December 2024
Department of Medicine, King's College Hospital NHS Foundation Trust, London, UK.
Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.
View Article and Find Full Text PDFJ Nutr Sci
December 2024
Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Renal sinus fat (RSF) crucially influences metabolic regulation, inflammation, and vascular function. We investigated the association between RSF accumulation, metabolic disorders, and nutritional status in obese individuals with hypertension. A cross-sectional study involved 51 obese hypertensive patients from Salamat Specialized Community Clinic (February-September 2022).
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