胰岛素受体底物2基因多态性与2型糖尿病及相关代谢的关联分析

The association of insulin receptor substrate 2 gene polymorphism with type 2 diabetes and its related metabolism

目的了解中国西南地区汉族人群胰岛素受体底物2(IRS-2)基因1057G/A多态性的分布;探讨该基因多态性与2型糖尿病的相关性;探讨2型糖尿病患者及糖耐量受损(IGT)患者的IRS-2基因型与糖脂代谢、胰岛素抵抗和胰岛β细胞功能的关系。方法应用聚合酶链反应-限制性片段长度多态性,对929例重庆及周边地区汉族人(包括462例2型糖尿病患者、164例IGT患者和303名正常对照者)的IRS-2基因1057G/A多态性进行测定,同时进行人体测量学、血脂、血糖、胰岛素、超敏C反应蛋白及非酯化游离脂肪酸的检测。分别用稳态模型胰岛素抵抗指数(HOMA-IR)和处置指数(DI)评估胰岛素抵抗和胰岛β细胞功能。结果糖尿病组A等位基因频率低于对照组(0.326 vs 0.388,X^2=6.19,P=0.01);AA基因型频率低于对照组,而GG基因型频率高于对照组(分别为0.104 vs 0.135,0.452 vs 0.360,X^2= 6.80,P<0.05)。Logistic回归分析表明GG基因型为2型糖尿病的危险因素,OR值为1.461(95%CI:1.082～1.973,P<0.05)。糖尿病组GG型的空腹血糖(FPG)和HOMA-IR值明显高于AA型(P<0.05)。IGT组GG型甘油三酯、FPG、空腹胰岛素、超敏C反应蛋白和HOMA-IR高于AA型(P<0.05);而DI指数低于AA型(P<0.05)。结论IRS-2基因1057G/A多态性可能与中国西南地区汉族人群2型糖尿病的发生有关。

Objective To study the genotype distribution of insulin receptor substrate-2 （IRS-2） gene 1057G/A polymorphism in Han population from Southwest China, and to explore its association with the metabolism of glucose and lipids, insulin resistance and islet β-cell function in type 2 diabetic patients and subjects with impaired glucose tolerance （IGT）. Methods A total of 929 Hans [ 462 patients with type 2 diabetes （DM group） and 164 subjects with IGT （IGT group） and 303 normal controls （NC group） ] from Chongqing and nearby regions were screened for 1057G/A polymorphism of IRS-2 gene by PCR-RFLP assay. Body mass index （ BMI ）, plasma glucose, serum insulin and lipid profile, high-sensitive C-reactive protein （hsCRP） and non-esterified fatty acid were measured. Homeostasis model assessment of insulin resistance （HOMA-IR） and disposition index （DI） were used to estimate insulin resistance and β-cell function respectively. Results In DM group, A allele frequency was significantly lower than that in NC group （0. 326 vs 0. 388, χ^2 =6.19, P =0.01 ）. Compared with NC group, AA genotype frequency was lower and GG genotype frequency was higher in DM group （0. 104 vs 0. 135 and 0.452 vs 0.360 respectively, χ^2 = 6.80, P 〈 0.05 ）. Logistic regression analysis showed that GG genotype might be a risk factor of type 2 diabetes, with OR = 1. 461 （95% CI： 1. 082-1. 973, P 〈 0.05）. In DM group, GG genotype carriers showed higher fasting plasma glucose and HOMA-IR than those of AA genotype （ P 〈 0.05 ）. In IGT group, GG genotype persons showed higher triglyceride, fasting plasma glucose, fasting insulin, hsCRP, HOMA- IR and lower DI than those of AA genotype （ P 〈 0.05 ）. Conclusion IRS-2 gene 1057G/A polymorphism appears to be associated with type 2 diabetes in Han population from Southwest China.