基于胰岛素抵抗代谢评分（METS-IR）评估的胰岛素抵抗风险影响高血压患病率的基因变异。

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

作者信息

Shine Bo-Kyung, Choi Ja-Eun, Park Young-Jin, Hong Kyung-Won

机构信息

Department of Family Medicine, Medical Center, Dong-A University, Busan 49201, Republic of Korea.

Institute of Advanced Technology, Theragen Health Co., Ltd., Seongnam 13493, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Nov 26;25(23):12690. doi: 10.3390/ijms252312690.

DOI:10.3390/ijms252312690

PMID:39684400

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11640995/

Abstract

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 ( < 5 × 10) 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.

摘要

胰岛素抵抗是包括高血压在内的心血管疾病的主要指标。胰岛素抵抗代谢评分（METS-IR）提供了一种简单且经济高效的方法来评估胰岛素抵抗。本研究旨在确定与按METS-IR评分水平分层的高血压患病率相关的基因变异。对韩国基因组与流行病学研究（KoGES）的数据进行了分析。METS-IR使用以下公式计算：ln[（2×空腹血糖（FBG）+甘油三酯（TG））×体重指数（BMI）]/ln[高密度脂蛋白胆固醇（HDL-C）]。根据参与者的METS-IR评分将其分为三分位数1（T1）和三分位数3（T3）。在这些三分位数组内，对高血压病例和非高血压对照进行全基因组关联研究（GWAS），并对年龄、性别和生活方式因素进行逻辑回归调整。在METS-IR三分位数组中，T1组的19774名参与者中有3517名（17.8%）患有高血压，而T3组的20374名参与者中有8653名（42.5%）患有高血压。共有113个单核苷酸多态性（SNP）在至少一个三分位数组中达到GWAS显著性阈值（<5×10），映射到六个不同的基因位点。值得注意的是，四个位点，rs11899121（chr2p24）、rs7556898（chr2q24.3）、rs17249754（ATP2B1）和rs1980854（chr20p12.2），在高METS评分组（T3）中与高血压显著相关。rs1085714（FGF5）在T1组和T3组中均显著，而rs671（ALDH2）仅在T1组中显著。GWAS确定了六个与高血压显著相关的基因位点，在METS-IR三分位数中有不同模式，突出了代谢背景在遗传易感性中的作用。这些发现强调了影响高血压患病率的关键遗传因素，并为该疾病潜在的代谢-遗传相互作用提供了见解。