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胰岛素受体底物2(IRS-2)基因G1057D多态性及其与肥胖的关系:亚洲印度人2型糖尿病易感性研究

The G1057D polymorphism of IRS-2 gene and its relationship with obesity in conferring susceptibility to type 2 diabetes in Asian Indians.

作者信息

Bodhini D, Radha V, Deepa R, Ghosh S, Majumder P P, Rao M R S, Mohan V

机构信息

Madras Diabetes Research Foundation and Dr Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India.

出版信息

Int J Obes (Lond). 2007 Jan;31(1):97-102. doi: 10.1038/sj.ijo.0803356. Epub 2006 Apr 25.

DOI:10.1038/sj.ijo.0803356
PMID:16652127
Abstract

OBJECTIVE

To investigate the association of insulin receptor substrate-2 (IRS-2) G1057D polymorphism with type 2 diabetes and obesity in Asian Indians.

METHODS

The study comprised of 1193 normal glucose tolerant (NGT) subjects and 1018 subjects with type 2 diabetes, aged >/=20 years with an average body mass index of 23.7+/-4.6 and 25.3+/-4.2 kg/m(2), respectively. The subjects were unrelated and randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study in Chennai in southern India. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay.

RESULTS

The genotype frequency of the IRS-2 G1057D polymorphism was significantly different between the NGT and type 2 diabetic groups (P=0.0007) in the total study subjects and among the obese subjects (P=0.00007). Logistic regression analysis showed that the DD genotype showed an increased susceptibility to diabetes with an odds ratio (adjusted for age and sex) of 2.19 (95% CI: 1.34-3.57, P=0.002) when compared to the GG+GD genotype, among the obese subjects, but not in non obese subjects. In order to explore possible interaction with obesity, logistic regression analysis was performed and the coefficient corresponding to the interaction parameter (genotype x obesity) was significant (P=0.0001).

CONCLUSION

In Asian Indians, the DD genotype increases susceptibility to type 2 diabetes by interacting with obesity.

摘要

目的

研究胰岛素受体底物-2(IRS-2)基因G1057D多态性与亚洲印度人2型糖尿病及肥胖症之间的关联。

方法

本研究纳入了1193例糖耐量正常(NGT)受试者和1018例2型糖尿病患者,年龄均≥20岁,平均体重指数分别为23.7±4.6和25.3±4.2kg/m²。这些受试者互不相关,是从印度南部金奈市的城乡流行病学研究(CURES)中随机选取的,该研究基于人群。采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对IRS-2基因的G1057D多态性进行基因分型。

结果

在全部研究对象以及肥胖受试者中,NGT组和2型糖尿病组之间IRS-2基因G1057D多态性的基因型频率存在显著差异(P = 0.0007)(肥胖受试者中P = 0.00007)。逻辑回归分析显示,在肥胖受试者中,与GG + GD基因型相比,DD基因型患糖尿病的易感性增加,比值比(校正年龄和性别后)为2.19(95%CI:1.34 - 3.57,P = 0.002),而非肥胖受试者中则无此现象。为探究与肥胖可能存在的相互作用,进行了逻辑回归分析,交互参数(基因型×肥胖)对应的系数具有显著性(P = 0.0001)。

结论

在亚洲印度人中,DD基因型通过与肥胖相互作用增加了患2型糖尿病的易感性。

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