携带rs7904519（TCF7L2）的冠心病患者持续面临患2型糖尿病的风险。

Coronary artery disease patients with rs7904519 (TCF7L2) are at a persistent risk of type 2 diabetes.

作者信息

Al Hageh Cynthia, O'Sullivan Siobhan, Platt Daniel E, Henschel Andreas, Chacar Stephanie, Gauguier Dominique, Abchee Antoine, Alefishat Eman, Nader Moni, Zalloua Pierre A

机构信息

Department of Molecular Biology and Genetics, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates.

Department of Molecular Biology and Genetics, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.

出版信息

Diabetes Res Clin Pract. 2024 Jan;207:111052. doi: 10.1016/j.diabres.2023.111052. Epub 2023 Dec 9.

DOI:10.1016/j.diabres.2023.111052

PMID:38072013

Abstract

AIMS

Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors.This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD.

METHODS

A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data.

RESULTS

Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519G: TCF7L2 and rs17608766C: GOSR2). The T2D susceptibility rs7904519G was associated with increased T2D risk, while the CAD susceptibility rs17608766C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results.

CONCLUSIONS

No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup.

摘要

目的

2型糖尿病（T2D）和冠状动脉疾病（CAD）常并存且共享遗传因素。本研究旨在调查CAD患者中T2D和CAD共同的遗传因素。

方法

采用三步关联方法：a）发现阶段，纳入943例合并T2D的CAD患者和1149例不合并T2D的CAD患者；b）排除阶段，排除CAD或T2D特异性变异；c）使用英国生物银行数据进行复制阶段。

结果

在CAD患者中，10个基因位点与T2D相关。3个变异是CAD或T2D特有的。5个变异在调整协变量后失去显著性，而2个单核苷酸多态性（SNP）在CAD患者中仍与T2D相关（rs7904519G：TCF7L2和rs17608766C：GOSR2）。T2D易感性rs7904519G与T2D风险增加相关，而CAD易感性rs17608766C与CAD患者的T2D呈负相关。这些关联在英国生物银行数据中得到复制，证实了结果。