Key result
In persons of African descent, carrying the endothelin-1 minor allele was associated with significantly greater aldosterone/renin ratios compared to European descent (coefficient 11.75).
Cohort (n=1,788)
Yes
Effect estimate: Coefficient 11.75 (95% CI 2.83-20.7)
p-value: p=0.010
Persons of African descent exhibit dysregulated aldosterone secretion that is modulated by EDN1 gene variants, suggesting they may particularly benefit from mineralocorticoid-receptor antagonists.
Highlights potential ancestry differences in aldosterone regulation; extends genetic associations but remains hypothesis-generating.
Compared with persons of European descent (ED), persons of African descent (AD) have lower aldosterone (ALDO) levels, with the assumption being that the increased cardiovascular disease (CVD) risk associated with AD is not related to ALDO. However, the appropriateness of the ALDO levels for the volume status in AD is unclear. We hypothesized that, even though ALDO levels are lower in AD, they are inappropriately increased, and therefore, ALDO could mediate the increased CVD in AD. To test this hypothesis, we analyzed data from HyperPATH - 1,788 individuals from the total cohort and 765 restricted to ED-to-AD in a 2:1 match and genotyped for the endothelin-1 gene (EDN1). Linear regression analyses with adjustments were performed. In the total and restricted cohorts, PRA, ALDO, and urinary potassium levels were significantly lower in AD. However, in the AD group, greater ALDO dysregulation was present as evidenced by higher ALDO/plasma renin activity (PRA) ratios (ARR) and sodium-modulated ALDO suppression-to-stimulation indices. Furthermore, EDN1 minor allele carriers had significantly greater ARRs than noncarriers but only in the AD group. ARR levels were modulated by a significant interaction between EDN1 and AD. Thus, EDN1 variants may identify particularly susceptible ADs who will be responsive to treatment targeting ALDO-dependent pathways (e.g., mineralocorticoid-receptor antagonists).
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Tan et al. (2017) conducted a cohort in Hypertension and Normotension (n=1,788). African descent with EDN1 minor allele vs. European descent was evaluated on Aldosterone/plasma renin activity ratio (ARR) on liberal salt diet (Coefficient 11.75, 95% CI 2.83-20.7, p=0.010). In persons of African descent, carrying the endothelin-1 minor allele was associated with significantly greater aldosterone/renin ratios compared to European descent (coefficient 11.75).
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