A CYP11B2 variant (rs7831617) is associated with lower blood pressure and a reduced risk of incident hypertension

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Abstract
Genetic variation contributes to interindividual differences in blood pressure regulation and the long-term risk of hypertension. CYP11B2, which encodes aldosterone synthase, is a key component of the renin‒angiotensin‒aldosterone system; however, longitudinal evidence linking common genetic variants near CYP11B2 to incident hypertension remains limited. We investigated genetic variation at the CYP11B2 locus in 8,840 participants from the Korean Genome and Epidemiology Study, a population-based cohort with up to 16 years of follow-up data. Following gene-centric screening, we identified rs7831617, a common noncoding variant located downstream of CYP11B2, with genotype frequencies of 46.4% (GG), 43.6% (GT), and 9.8% (TT). Associations of rs7831617 with baseline blood pressure, plasma renin concentrations, prevalent hypertension, and incident hypertension were examined via multivariable regression and discrete-time survival analyses. In addition, metabolomic profiling was conducted in a subset of participants to explore genotype-dependent metabolic differences. The rs7831617 T allele was nominally associated with higher plasma renin concentrations and a lower risk of incident hypertension during follow-up (adjusted hazard ratio 0.93, 95% confidence interval 0.88-0.99), whereas no association was observed with prevalent hypertension at baseline. Metabolomic profiling revealed no global genotype-dependent metabolic shifts, with only six metabolites (glutamate, alanine, asparagine, PC ae C34:1, PC ae C42:4, and PC ae C44:5) showing nominal associations with genotype. Although several clinical and metabolomic phenotypes showed nominal associations with rs7831617, none remained significant after correction for multiple testing. These findings suggest a potential association of rs7831617, a common noncoding variant adjacent to CYP11B2, with lower blood pressure and a reduced long-term risk of hypertension.
Funding Information
  • National Research Foundation of Korea (RS-2023-00210819)
  • the Daejeon and Chungcheong Branch of the Korean Endocrine Society

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