An explorative epigenome-wide association study of plasma renin and aldosterone concentration in a Ghanaian population: the RODAM study

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 conc...

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Published in:Clinical epigenetics 2022-12, Vol.14 (1), p.159-159, Article 159
Main Authors: van der Linden, Eva L, Halley, Adrienne, Meeks, Karlijn A C, Chilunga, Felix, Hayfron-Benjamin, Charles, Venema, Andrea, Garrelds, Ingrid M, Danser, A H Jan, van den Born, Bert-Jan, Henneman, Peter, Agyemang, Charles
Format: Article
Language:English
Subjects:
Aldosterone
Aldosterone - blood
Analysis
Angiotensin
Arteriosclerosis
Atherosclerosis
Blood pressure
Body mass index
Corticosteroids
Diabetes
Diabetes mellitus
DNA Methylation
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Epigenome
Ghana
Humans
Hypertension
Hypertension - genetics
Kidneys
Laboratories
Methylation
Nerve Tissue Proteins
Normal distribution
Obesity
Plasma
Population studies
Potassium Channels, Sodium-Activated
Quality control
Regression analysis
Renin
Renin - blood
Risk factors
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Summary: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). 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. 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. 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.
ISSN:1868-7075
1868-7083
1868-7083
1868-7075
DOI:10.1186/s13148-022-01378-5