胰岛素受体底物-1和葡萄糖转运蛋白基因多态性与糖尿病及糖尿病肾病的关系

Insulin receptor substrate1 and glucose transporter gene polymorphisms in noninsulindependent diabetes mellitus

目的探讨胰岛素受体底物１（ＩＲＳ１）和葡萄糖转运蛋白（ＧＬＵＴ１）基因多态性与糖尿病及其糖尿病肾病的关系。方法应用ＰＣＲＲＦＬＰ方法对１３１例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者ＩＲＳ１和ＧＬＵＴ１基因多态性进行了观察，并结合肾脏病变、体重指数（ＢＭＩ）和胰岛素敏感指数（ＩＳＩ）进行了分析。结果ＩＲＳ１基因多态性在ＮＩＤＤＭ和正常人中的分布没有明显差异。ＮＩＤＤＭ患者ＧＬＵＴ１基因ＸｂａⅠ（＋／－）基因型和ＸｂａⅠ（－）等位基因的发生率明显高于正常人。ＸｂａⅠ（＋／－）基因型和ＸｂａⅠ（－）等位基因在糖尿病肾病（７５％和４４％）的发生频率明显高于不伴肾病者（４４％和２９％）和正常人（３３％和２１％），而ＧＬＵＴ１基因多态性在不伴肾病者与正常人之间无明显差异。ＩＳＩ在ＸｂａⅠ（＋／＋）、ＸｂａⅠ（＋／－）和ＸａｂⅠ（－／－）３种基因，分别为０８２、０７６和０４８；ＧＬＵＴ１基因各基因型患者间ＢＭＩ差异无显著意义。结论ＧＬＵＴ１基因ＸｂａⅠ（－）等位基因不仅与糖尿病肾病的易感性相关，而且可能还与患者胰岛素抵抗的发生有关。

Objective To evaluate the role of insulin receptor substrate1 (IRS1) and glucose transporter1 (GLUT1) gene polymorphisms in Chinese patients with noninsulindependent diabetes mellitus (NIDDM) and diabetic nephropathy (DN).Methods Aminoacid polymorphism in codon 972 of IRS1 gene and the polymorphic XbaⅠ site of GLUT1 gene were analyzed by PCRRFLP in 131 patients with NIDDM and 124 normal subjects. DN was defined as persistent albuminuria and/or impaired renal function, without known cause of renal diseases other than diabetes. Insulin sensitivity index (ISI) and body mass index (BMI) were also calculated. Results The distribution of IRS1 gene polymorphism showed no difference between patients with NIDDM and normal controls. The frequencies of XbaⅠ(+/-) genotype (59% vs. 33%, P<0.01) and XbaⅠ(-) allele (37% vs. 21%, P<0.01) were significantly higher in NIDDM patients than in normal subjects. To further explore the linkage of GLUT1 gene polymorphism with DN, we examined the GLUT1 genotype of NIDDM patients with or without renal damage. The frequency of XbaⅠ(+/-) genotype (75%vs. 44%,P<0.01) and XbaⅠ(-) allele (44% vs. 29%,P<0.05) was significantly higher in NIDDM patients with diabetic nephropathy than either those without nephropathy or normal subjects. However, there were no significant differences of GLUT1 genotype and allele frequency in NIDDM patients without nephropathy and normal controls. The presence of XbaⅠ(-) allele appeared to have a strong association with the development of diabetic nephropathy. The odds ratio was 1.915, and the 95% confidence interval was 1.0443.514. The association of XbaⅠ(-) allele of GLUT1 gene with NIDDM partly reflected their close association with DN. Although there was no correlation between the gene polymorphism of GLUT1 and BMI, patients carrying the XbaⅠ(-) allele showed a lower ISI. Conclusion No association was found between the gene polymorphism of IRS1 and NIDDM. THe XbaⅠ(-) allele of GLUT1 gene might be taken as a genetic marker of NIDDM with diabetic nephropathy and this genetic susceptibility appears to be associated with the insulin resistance in patients with NIDDM.