Key result
Low plasma renin linked to ~9 percentage points higher incidence of new-onset hypertension.
Why the study?
The renin-angiotensin system regulates vascular resistance and blood volume, and this study aimed to examine the genetic predisposition of plasma renin concentration influencing future hypertension incidence.
Does low plasma renin concentration and specific genetic polymorphisms (like rs12336898) predict new-onset hypertension in normotensive adults?
Cohort (n=5,211)
Yes
Does low plasma renin concentration and specific genetic polymorphisms (like rs12336898) predict new-onset hypertension in normotensive adults?
Low renin levels combined with specific genetic polymorphisms (like rs12336898 in SPTAN1) may identify individuals at a higher risk of developing salt-sensitive hypertension, particularly in high-sodium intake populations like Korea.
Low-renin normotensives showed higher hypertension incidence; hypothesis-generating for SPTAN1 genotyping in observational cohorts, pending prospective validation.
The renin-angiotensin system (RAS) is a crucial regulator of vascular resistance and blood volume in the body. This study aimed to examine the genetic predisposition of the plasma renin concentration influencing future hypertension incidence. Based on the Korean Genome and Epidemiology Cohort dataset, 5211 normotensive individuals at enrollment were observed over 12 years, categorized into the low-renin and high-renin groups. We conducted genome-wide association studies for the total, low-renin, and high-renin groups. Among the significant SNPs, the lead SNPs of each locus were focused on for further interpretation. The effect of genotypes was determined by logistic regression analysis between controls and new-onset hypertension, after adjusting for potential confounding variables. During a mean follow-up period of 7.6 years, 1704 participants (32.7%) developed hypertension. The low-renin group showed more incidence rates of new-onset hypertension (35.3%) than the high-renin group (26.5%). Among 153 SNPs in renin-related gene regions, two SNPs (rs11726091 and rs8137145) showed an association in the high-renin group, four SNPs (rs17038966, rs145286444, rs2118663, and rs12336898) in the low-renin group, and three SNPs (rs1938859, rs7968218, and rs117246401) in the total population. Most significantly, the low-renin SNP rs12336898 in the SPTAN1 gene, closely related to vascular wall remodeling, was associated with the development of hypertension (p-value = 1.3 × 10−6). We found the candidate genetic polymorphisms according to blood renin concentration. Our results might be a valuable indicator for hypertension risk prediction and preventive measure, considering renin concentration with genetic susceptibility.
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Lee et al. (2022) conducted a cohort in Normotensive (n=5,211). Low plasma renin concentration and SPTAN1 gene polymorphism (rs12336898) vs. High plasma renin concentration was evaluated on New-onset hypertension (p=1.3 × 10−6). Low plasma renin concentration was associated with a higher incidence of new-onset hypertension (35.3% vs 26.5%), with the SPTAN1 gene SNP rs12336898 demonstrating the most significant genetic association (p = 1.3 × 10−6).
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