北方汉族2型糖尿病人胰岛素受体底物1基因多态性的研究

Gene polymorphism of insulin receptor substrate-1 in Northern Chinese Han pedigrees with type 2 diabetes mellitus

目的:研究胰岛素受体底物1(IRS - 1)基因变异在中国北方汉族2型糖尿病人发病中的作用。方法:应用聚合酶链反应-序列特异性引物(PCR -SSP)技术对80例无血缘关系的辽宁地区糖尿病病人和80例正常人IRS - 1基因的80 4、971密码子的核苷酸多态性进行检测。结果:2型糖尿病人的IRS - 1基因第80 4密码子GCG基因型频率明显高于正常人(分别为0 . 2 0 0和0 .0 6 2 ,P <0 .0 1)。第971位密码子AGG基因型在2型糖尿病病人和正常人分别为2例和1例。在2型糖尿病中,第80 4密码子GCG基因型和第971位密码子AGG基因型的患者胰岛素敏感指数明显下降,但携带不同基因型的患者间体重指数无明显差异。结论:2型糖尿病的IRS - 1基因变异与胰岛素抵抗密切相关;胰岛素抵抗可能是2型糖尿病发病的重要原因,而IRS - 1基因变异是其重要的遗传背景之一。

AIM: To investigate the role of gene poly mo rphisms of insulin receptor substrate-1 (IRS-1) in northern Chinese Han pedigree s with type 2 diabetes mellitus (DM). METHODS: Polymorphisms in codon 804 and 971 of IRS-1 gene in 80 unrelated patients with type 2 DM and 80 control subjects were analyzed by polym erase chain reaction-sequence specific primer(PCR-SSP) technique followed by pol yacrylamide gel electrophoresis and silver staining. RESULTS: The frequencies (GCA→GCG) in codon 804 of IRS-1 gene w ere significantly higher in type 2 DM than normal subjects(0.200 vs 0.062, P<0.01). The mutation (GGG→AGG) in codon 971 was found in 2 patients with type 2 DM and 1 normal subject. Patients carrying these variations showed the lower insulin-sensitivity index, but no association was found between the gene p olymorphism of IRS-1 and body mass index. CONCLUSIONS: There may be a relation between nucleotide variatio ns of IRS-1 gene and insulin resistance (or type 2 DM). GCG genotype in codon 80 4 and AGG genotype in codon 971 may be genetic markers for development of type 2 DM and insulin resistance in northern Chinese Han pedigrees.