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。
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 Abstract: 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.
Key words: glucagon-like peptide-1 receptor (GLP-1R), single nucleotide polymorphism (SNP), rs3765467, type 2 diabetes mellitus (T2DM) PDF全文下载地址:
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