全基因组和候选基因关联分析确定了2型糖尿病患者高血压的一个14个单核苷酸多态性组合。

Genome-Wide and Candidate Gene Association Analyses Identify a 14-SNP Combination for Hypertension in Patients With Type 2 Diabetes.

作者信息

Cheng Chi-Fung, Hsieh Ai-Ru, Liang Wen-Miin, Chen Ching-Chu, Chen Chien-Hsiun, Wu Jer-Yuarn, Lin Ting-Hsu, Liao Chiu-Chu, Huang Shao-Mei, Huang Yu-Chuen, Ban Bo, Lin Ying-Ju, Tsai Fuu-Jen

机构信息

Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.

Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.

出版信息

Am J Hypertens. 2021 Jun 22;34(6):651-661. doi: 10.1093/ajh/hpaa203.

DOI:10.1093/ajh/hpaa203

PMID:33276381

Abstract

BACKGROUND

High blood pressure is common and comorbid with type 2 diabetes (T2D). Almost 50% of patients with T2D have high blood pressure. Patients with both conditions of hypertension (HTN) and T2D are at risk for cardiovascular diseases and mortality. The study aim was to investigate genetic risk factors for HTN in T2D patients.

METHODS

This study included 999 T2D (cohort 1) patients for the first genome scan stage and 922 T2D (cohort 2) patients for the replication stage. Here, we investigated the genetic susceptibility and cumulative weighted genetic risk score for HTN in T2D patients of Han Chinese descent in Taiwan.

RESULTS

Thirty novel genetic single nucleotide polymorphisms (SNPs) were associated with HTN in T2D after adjusting for age and body mass index (P value <1 × 10-4). Eight blood pressure-related and/or HTN-related genetic SNPs were associated with HTN in T2D after adjusting for age and body mass index (P value <0.05). Linkage disequilibrium and cumulative weighted genetic risk score analyses showed that 14 of the 38 SNPs were associated with risk of HTN in a dose-dependent manner in T2D (Cochran-Armitage trend test: P value <0.0001). The 14-SNP cumulative weighted genetic risk score was also associated with increased regression tendency of systolic blood pressure in T2D (SBP = 122.05 + 0.8 × weighted genetic risk score; P value = 0.0001).

CONCLUSIONS

A cumulative weighted genetic risk score composed of 14 SNPs is important for HTN, increased tendency of systolic blood pressure, and may contribute to HTN risk in T2D in Taiwan.

摘要

背景

高血压很常见，且与2型糖尿病（T2D）合并存在。近50%的T2D患者患有高血压。同时患有高血压（HTN）和T2D的患者存在心血管疾病和死亡风险。本研究旨在调查T2D患者中高血压的遗传风险因素。

方法

本研究包括999名T2D患者（队列1）用于首个基因组扫描阶段，以及922名T2D患者（队列2）用于复制阶段。在此，我们调查了台湾汉族血统T2D患者中高血压的遗传易感性和累积加权遗传风险评分。

结果

在调整年龄和体重指数后，30个新的遗传单核苷酸多态性（SNP）与T2D患者的高血压相关（P值<1×10-4）。在调整年龄和体重指数后，8个与血压相关和/或与HTN相关的遗传SNP与T2D患者的高血压相关（P值<0.05）。连锁不平衡和累积加权遗传风险评分分析表明，38个SNP中的14个与T2D患者高血压风险呈剂量依赖性相关（ Cochr an-Armitage趋势检验：P值<0.0001）。14-SNP累积加权遗传风险评分也与T2D患者收缩压回归趋势增加相关（收缩压=122.05+0.8×加权遗传风险评分；P值=0.0001）。