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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 investigate the distribution of 1057G / A polymorphism of insulin receptor substrate 2 (IRS-2) gene in Chinese Han population in Southwest China. To investigate the association between polymorphism of this gene and type 2 diabetes mellitus (T2DM) IRS-2 genotypes in patients with impaired (IGT) glucose and lipid metabolism, insulin resistance and pancreatic β-cell function. Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphism of IRS-2 gene 1057G in 929 Han and surrounding areas in Chongqing (including 462 type 2 diabetic patients, 164 IGT patients and 303 normal controls) / A polymorphisms were measured at the same time, anthropometry, blood lipids, blood glucose, insulin, high-sensitivity C-reactive protein and non-esterified free fatty acid detection. Insulin resistance and islet β-cell function were assessed using homeostatic model insulin resistance index (HOMA-IR) and treatment index (DI), respectively. Results The frequency of allele A in diabetic group was lower than that in control group (0.326 vs 0.388, X ~ 2 = 6.19, P = 0.01). The frequency of AA genotype was lower than that of control group, while the frequency of GG genotype was higher than that of control group vs 0.135, 0.452 vs 0.360, X ~ 2 = 6.80, P <0.05). Logistic regression analysis showed that GG genotype was a risk factor for type 2 diabetes with OR of 1.461 (95% CI: 1.082-1.973, P <0.05). The fasting blood glucose (FPG) and HOMA-IR of GG type in diabetic group were significantly higher than those in AA type (P <0.05). GG triglycerides, FPG, fasting insulin, high sensitivity C-reactive protein and HOMA-IR in IGT group were higher than those in AA group (P <0.05), while DI index was lower than that in AA group (P <0.05). Conclusion The 1057G / A polymorphism of IRS-2 gene may be related to the occurrence of type 2 diabetes in Han population of southwest China.