胰岛素抵抗的分子遗传学病因

Molecular etiology of insulin resistance

目的探讨中国人群胰岛素受体底物１（ＩＲＳ１）基因、β３肾上腺素受体（β３ＡＲ）基因突变与胰岛素抵抗的关系。方法对２８１例病人通过糖耐量试验分为糖耐量正常组、糖耐量低减组及糖尿病组，分别对之进行ＩＲＳ１基因、β３ＡＲ基因多态性分析。结果糖尿病者和糖耐量正常者相比，ＩＲＳ１基因、β３ＡＲ基因的基因型频率及等位基因频率存在明显差异；多元回归分析发现：胰岛素水平和ＩＲＳ１基因、β３ＡＲ基因多态性显著相关。非条件多因素Ｌｏｇｉｓｔｉｃ回归模型发现：糖尿病和β３ＡＲ基因多态性有明显关系。结论β３ＡＲ基因突变可能是与胰岛素抵抗有关疾病的共有危险因素。

Objective To explore the relation of insulin receptor substrate1 (IRS1) gene and β_3adrenergic receptor (β3AR) gene varition with insulin resistance. Methods The polymorphism of the IRS1 gene and β3 AR gene was studied in 281 subjects, who were divided into 3 groups: normal glucose tolerance, impaired glucose tolerance, diabetes mellitus. Results The frequency of codon 972 mutation of IRS1 gene and codon 64 mutation of β3AR gene in diabetes mellitus was increased as compared with that in subjects having normal glucose tolerance. In multiple regression analyses, the level of insulin was related to polymorphism of IRS1 gene and β3AR gene. In the model of multiplefactor nonconditional Logistic regression analyses, diabetes mellitus had relation with polymorphism of β3AR gene. Conclusion The codon 64 mutation of β3AR gene might be the risk factor of insulin resistance. 