The insulin receptor substrate-1 Gly972Arg polymorphism is not associated with Type 2 diabetes mellitus in two population-based studies
The insulin receptor substrate-1 Gly972Arg polymorphism is not associated with Type 2 diabetes mellitus in two population-based studies
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DOI：
10.1111/j.1464-5491.2004.01229.x
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Feskens, EJM
中科院分区：
文献类型：
--
作者：
van Dam, RM;Hoebee, B;Feskens, EJM
胰岛素受体底物-1 （IRS-1）基因是研究最多的2型糖尿病候选基因之一，但研究结果并不一致。这可能是由于研究规模一般较小，或者与胰岛素敏感性研究表明的身体脂肪相互作用。本研究的目的是验证IRS-1 Gly972Arg变异增加2型糖尿病风险的假设。方法我们进行了两项基于人群的大型研究，包括725例病例和742例对照受试者，他们是40-70岁的荷兰高加索男性和女性。我们计算了经体重指数、研究中心、性别和年龄调整后的比值比。结果在第一项研究中，Arg等位基因携带者新发现（OR 0.49, 95% CI 0.24-1.01）或治疗（OR 0.71, 0.37-1.35） 2型糖尿病的患病率没有更高，在第二项研究中，Arg等位基因携带者葡萄糖耐受不良的患病率也没有更高（OR 1.07, 0.71-1.59）。与Gly/Gly基因型相比，携带Arg等位基因的总优势比为0.86（0.62-1.17）。这种关联在肥胖程度上没有明显差异。此外，Arg变异与身体质量指数、腰围、血浆高密度脂蛋白、总胆固醇或高血压的有害值无关。我们的研究结果表明，IRS-1 Gly972Arg变异不会显著增加普通2型糖尿病或肥胖人群患2型糖尿病的风险。
Aims The insulin receptor substrate-1 (IRS-1) gene is among the most frequently studied candidate genes for Type 2 diabetes, but findings have been inconsistent. This may have been due to generally small study sizes, or to interaction with body fatness as suggested by studies of insulin sensitivity. The aim of this study was to test the hypothesis that the IRS-1 Gly972Arg variant increases risk of Type 2 diabetes.Methods We conducted two large population-based studies including a total of 725 cases and 742 control subjects, who were Caucasian Dutch men and women aged 40-70 years. We calculated odds ratios adjusted for body mass index, study centre, sex and age.Results Carriers of the Arg allele did not have a higher prevalence of newly detected (OR 0.49, 95% CI 0.24-1.01) or treated (OR 0.71, 0.37-1.35) Type 2 diabetes in the first study, or a higher prevalence of glucose intolerance (OR 1.07, 0.71-1.59) in the second study. The summary odds ratio was 0.86 (0.62-1.17) for carrying the Arg allele as compared with the Gly/Gly genotype. Associations did not differ appreciably by degree of obesity. Also, the Arg variant was not associated with detrimental values for body mass index, waist circumference, plasma HDL-and total cholesterol or hypertension.Conclusions Our findings indicate that the IRS-1 Gly972Arg variant does not substantially increase risk of common Type 2 diabetes, or Type 2 diabetes in obese persons.