The Genetic Variants Influencing Hypertension Prevalence Based on the Risk of Insulin Resistance as Assessed Using the Metabolic Score for Insulin Resistance (METS-IR)

Insulin resistance is a major indicator of cardiovascular diseases, including hypertension. The Metabolic Score for Insulin Resistance (METS-IR) offers a simplified and cost-effective way to evaluate insulin resistance. This study aimed to identify genetic variants associated with the prevalence of hypertension stratified by METS-IR score levels. Data from the Korean Genome and Epidemiology Study (KoGES) were analyzed. The METS-IR was calculated using the following formula: ln [(2 × fasting blood glucose (FBG) + triglycerides (TG)) × body mass index (BMI)]/ ln [high-density lipoprotein cholesterol (HDL-C)]. The participants were divided into tertiles 1 (T1) and 3 (T3) based on their METS-IR scores. Genome-wide association studies (GWAS) were performed for hypertensive cases and non-hypertensive controls within these tertile groups using logistic regression adjusted for age, sex, and lifestyle factors. Among the METS-IR tertile groups, 3517 of the 19,774 participants (17.8%) at T1 had hypertension, whereas 8653 of the 20,374 participants (42.5%) at T3 had hypertension. A total of 113 single-nucleotide polymorphisms (SNPs) reached the GWAS significance threshold (<i>p</i> < 5 × 10^-8) in at least one tertile group, mapping to six distinct genetic loci. Notably, four loci, rs11899121 (chr2p24), rs7556898 (chr2q24.3), rs17249754 (ATP2B1), and rs1980854 (chr20p12.2), were significantly associated with hypertension in the high-METS-score group (T3). rs10857147 (FGF5) was significant in both the T1 and T3 groups, whereas rs671 (ALDH2) was significant only in the T1 group. The GWASs identified six genetic loci significantly associated with hypertension, with distinct patterns across METS-IR tertiles, highlighting the role of metabolic context in genetic susceptibility. These findings underscore critical genetic factors influencing hypertension prevalence and provide insights into the metabolic-genetic interplay underlying this condition.