胰升糖素样肽1受体基因多态性与2型糖尿病代谢指标的相关性研究

Association between glucagon-like peptide-1 receptor gene polymorphisms and metabolic markers in type 2 diabetic patients

目的 探讨中国汉族2型糖尿病人群胰升糖素样肽1受体基因(GLP-1R)rs10305420和rs3765467位点基因多态性的分布特征,及对体重指数(BMI)、血糖、血脂等代谢指标的影响.方法 采用Sanger双脱氧终止测序法检测137例中国汉族2型糖尿病患者GLP-1R rs3765467、rs10305420位点的基因型,分析其与BMI、血脂和血糖的关联性及人种特征.结果 GLP-1R两位点的基因多态性分布均符合Hardy-Weinberg平衡.rs10305420 T等位基因携带者的高密度脂蛋白(HDL-C)水平显著低于CC基因型(1.00±0.18对1.09±0.22,P=0.02),rs3765467 A等位基因携带者的三酰甘油(TG)水平高于GG型(2.75±2.19对2.07±1.36,P=0.03).rs10305420 C/T位点的最小等位基因频率(MAF)低于欧洲人群,rs3765467 G/A的MAF高于欧洲和非洲人群.结论 GLP-1R基因rs10305420和rs3765467两位点的多态性与2型糖尿病患者的血脂水平有显著关联,且等位基因频率分布存在种族差异.

Objective To investigate the distribution of polymorphisms of glucagon-like peptide-1 receptor gene(GLP-1R)rs10305420 and rs3765467 in Chinese Han type 2 diabetic patients,and the effects on body weight,blood glucose and serum lipid levels.Methods Two SNPs of GLP-1R rs3765467 and rs10305420 were genotyped by Sanger dideoxy termination sequencing method.The racial difference and the association between the gene polymorphisms and the metabolic markers including BMI,serum lipids and blood glucose were analyzed.Results The distribution of gene polymorphisms was consistent with the Hardy-Weinberg equilibrium.High-density lipoprotein(HDL-C)levels were significantly lower in the rs10305420 T allele carriers than in the CC genotype(1.00±0.18 vs 1.09±0.22,P=0.02).The triglyceride(TG)level of the rs3765467 A allele carrier was higher than that of the GG type(2.75±2.19 vs 2.07±1.36,P=0.03).The allele frequency of rs10305420 C/T was highly statistically significant compared with European population(P=0.0003).The allele frequency of rs3765467 G/A was statistically different from that of European and African populations(P<0.01).Conclusions The two genetic polymorphisms were significantly associated with lipid levels in patients with type 2 diabetes,and there was a significant racial difference in the frequency distribution of the two variants.