OBJECTIVETo investigate the relationship between the G1057D variants of insulin receptor substrate-2(IRS2) gene and type 2 diabetes mellitus (T2DM) in subjects.

METHODSFour 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).

CONCLUSIONThe relationships between G1057D variants of IRS2 and T2DM are mediated by obesity.