胰高血糖素样肽1受体基因rs3765467变异与2型糖尿病的关联研究  

Association study of variation of glucagon-like peptide-1 receptor gene rs3765467 and type 2 diabetes mellitus

作　　者：张静静 祝超瑜[2] 肖元元[2] 蒋伏松[2] 高清歌[2] 方云云 魏丽[2] ZHANG Jing-jing;ZHU Chao-yu;XIAO Yuan-yuan;JIANG Fu-song;GAO Qing-ge;FANG Yun-yun;WEI Li(Department of Biology,Shanghai Ocean University,College of Fisheries and Life Science,Shanghai 201306,China;Department of Endocrinology and Metabolism,Shanghai Sixth People′s Hospital,Shanghai Jiao Tong University,Shanghai 200233,China)

机构地区：[1]上海海洋大学水产与生命学院生物系,上海201306 [2]上海交通大学附属第六人民医院内分泌代谢科,上海200233

出　　处：《上海交通大学学报（医学版）》2021年第9期1215-1221,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市自然科学基金(20ZR1442500);浦东新区卫生计生科研联合攻关项目(PW2018D-14)。

摘　　要：目的·探讨胰高血糖素样肽1受体(glucagon-like peptide-1 receptor,GLP-1R)外显子单核苷酸多态性(single nucleotide polymorphisms,SNPs)与2型糖尿病(type 2 diabetes mellitus,T2DM)的关系。方法·选取318例T2DM患者和145例非糖尿病对照者为研究对象(汉族),利用多重PCR靶向重测序Hi-Reseq技术检测GLP-1R基因外显子的SNPs位点,分析组间基因型、等位基因频率分布及临床特征的差异。结果·检测分析发现了23个SNPs位点,其中GLP-1R rs3765467(G/A)位点多态性与T2DM显著相关(P=0.005),与GG基因型携带者相比GA+AA基因型者患病风险降低(OR=0.502,95%CI 0.305~0.829,P=0.007),其中男性人群GA+AA基因型者患病风险显著降低(OR=0.403,95%CI 0.186~0.871,P=0.021)。临床特征关联分析表明,GA+AA基因型携带者糖化白蛋白水平低于GG基因型者(P=0.048)。结论·GLP-1R基因rs3765467位点多态性与上海地区汉族人群T2DM相关;次要等位基因A可能有助于维持血糖稳态,是T2DM的保护因素,这种保护性在男性中尤为显著。Objective·To investigate the association of single nucleotide polymorphisms(SNPs)in the glucagon-like peptide-1 receptor(GLP-1R)gene with type 2 diabetes mellitus(T2DM).Methods·A total of 318 Han patients with T2DM and 145 non-diabetic controls in Shanghai were enrolled.The polymorphisms of GLP-1R gene were detected with multiplex PCR-High throughput resequencing.Differences in frequencies of genotypes and alleles,as well as other clinical variables between the two groups were analyzed.Results·Twenty three SNPs were detected.The polymorphism of GLP-1R rs3765467(G/A)was significantly associated with T2DM(P=0.005).Compared with GG genotype carriers,GA+AA genotype carriers had a lower risk of T2DM(OR=0.502,95%CI 0.305-0.829,P=0.007),while GA+AA genotype carriers had a significantly lower risk of T2DM(OR=0.403,95%CI 0.186-0.871,P=0.021)in the male population.Association analysis of clinical feature showed that the glycosylated albumin level of GA+AA genotype carriers was lower than that of GG genotype carriers(P=0.048).Conclusion·GLP-1R rs3765467 polymorphism is associated with T2DM in Shanghai Han population.Minor allele A contributes to maintaining blood glucose homeostasis and is a protective factor for T2DM,especially in men.

关 键 词：胰高血糖素样肽1受体 单核苷酸多态性 rs3765467 2型糖尿病 

分 类 号：R587.1[医药卫生—内分泌]