Analysis of Insulin Receptor Substrate-1 (IRS-1) Gene Mutations in Non-Insulin Dependent Diabetes Mellitus.

结果总结如下：1。PCR-SSCP分析：对94例被试（47例NIDDM和47例对照）进行IRS-1基因全编码区筛选，鉴定出7个SSCP多态性。序列分析：通过序列分析，确定每个SSCP多态性对应4个错义突变和3个沉默突变。5个多态性{P170R、M209T、S809F、Leu^<142> (CTT*CTC)、Gly^<625> (GGC*GGT)}为新发现多态性，2个多态性{Ala^<804> (GCA*GCG)、G971R}为已有报道。IRS-1基因多态性对胰岛素抵抗发展的贡献评估：4种IRS-1错义突变在NIDDM中的发生率显著高于对照组（23.4%vs.8.5%， P<0.05）， 2种错义突变（M209T,S809F）仅在NIDDM中发现。与没有多态性的对照组相比，具有IRS-1多态性的NIDDM和对照组在正糖钳夹期间的平衡葡萄糖输注率（gils）平均分别下降了29.5%和22.0%，尽管由于研究对象较少，它们没有统计学意义。

The results are summarized as follows.1.PCR-SSCP analysis : The entire coding region of IRS-1 gene of 94 subjiects (47 NIDDM and 47 controls) was screened by PCR-SSCP analysis, and seven SSCP polymorphisms were identified.2.Sequence analysis : By sequence analysis, 4 missense and 3 silent mutations corresponding to each SSCP polymorphisms were determined. Five polymorphisms {P170R,M209T,S809F,Leu^<142> (CTT*CTC), Gly^<625> (GGC*GGT) } were novel and two were previously reported {Ala^<804> (GCA*GCG), G971R}.3.Evaluation of contribution of the IRS-1 gene polymorphisms to the development of insulin resistance : The prevalence of the four IRS-1 missense mutations taken together was significantly higher in NIDDM than that in control (23.4%vs.8.5%, P<0.05), and two missense mutations (M209T,S809F) were found only in NIDDM.The equilibrated glucose infusion rates (GIRs) during an euglycemic clamp in NIDDM and controls with the IRS-1 polymorphisms decreased by 29.5%and 22.0%, respectively in average when compared to those in comparable groups without polymorphisms, although they were not statistically significant probably due to the small number of subjects studied.