IRS2基因G1057D变异与中国汉族人肥胖型2型糖尿病的相关性

目的 研究IRS2基因G1057D突变与中国汉族人2型糖尿病（type 2 diabetes mellitus，T2DM）的相关性。方法 选取辽宁汉族人T2DM组218例，健康对照组221名，各分为肥胖和非肥胖两个亚组。应用聚合酶链反应-限制性片段长度多态性方法筛查IRS2 G1057D突变并探讨与T2DM的相关性。结果 （1）IRS2 G1057D总突变频率为29％。非肥胖DM组DD型频率显著低于非肥胖对照组，Logistic回归分析显示DD型OR值为0．265；而肥胖DM组DD型频率则显著高于肥胖对照组，Logistic回归分析显示DD型的OR值为3．991。（2）在非肥胖亚组：DM组DD型的WHR高于同组GG型（P〈0．01）；对照组DD型的FPG及2hCP低于同组GG型（P〈0．05，P〈0．01），HOMA-B高于同组GG型（P〈0．01）。在肥胖亚组：DM组DD型的WHR、HOMA-IR及2hPG、2hINS、2hCP均高于同组GG型，HOMA-B低于同组GG型；对照组DD型的WHR、2hINS、HOMA-IR及HOMA-B也分别高于及低于同组GG型（均P〈0．05）。结论 IRS2基因G1057D突变以肥胖为中介与他DM相关联。

Study on the relationship between G1057D variants of IRS2 gene and obese T2DM in Chinese Han subjects

OBJECTIVE: To investigate the relationship between the G1057D variants of insulin receptor substrate-2(IRS2) gene and type 2 diabetes mellitus (T2DM) in subjects. METHODS: Four hundred and thirty-nine Chinese Han subjects, including 218 patients with T2DM and 221 normal controls, were selected from the Hans in the Liaoning area, and each group was divided into two subgroups according to body mass index. The G1057D variants of IRS2 were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and their relationships with T2DM were analyzed. RESULTS: (1) The frequency of G1057D variant was 29% in all subjects. The frequency of DD genotype was significantly lower in non-obese DM group than in non-obese control group. The Logistic regression analysis showed that the odds ratio of DD genotype was 0.265. The frequency of DD genotype was significantly higher in obese DM group than in obese control group. The Logistic regression analysis showed that the odds ratio of DD genotype was 3.991. (2) In the non-obese control group, the FPG and 2hCP of DD genotypes were lower than those of GG genotypes (P< 0.05, P< 0.01), the HOMA-B of DD genotypes was higher than that of GG genotype (P< 0.01). In the non-obese DM group, the waistline/hip ratio (WHR) of DD genotypes was higher than that of GG genotypes(P< 0.01). In the obese DM group, the WHR, HOMA-IR, 2hPG, 2hINS and 2hCP levels of DD genotypes were higher than those of GG genotypes, while the level of HOMA-B of DD genotypes was lower than that of GG genotypes. In the obese control group, the WHR, HOMA-IR, 2hPG, 2hINS and 2hCP levels of DD genotype were higher than those of GG genotype, and the HOMA-B level of DD genotype was lower than that of GG genotypes (P< 0.05). CONCLUSION: The relationships between G1057D variants of IRS2 and T2DM are mediated by obesity.