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

结果如下：1.PCR-SSCP分析：对94个亚组(47个NIDDM和47个对照组)的IRS-1基因全长编码区进行了筛选，发现了7个SSCP多态性。2.序列分析：通过序列分析，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^&lt；142&gt；(CTT*CTC)，Gly^&lt；625&gt；(GGC*ggt)}是新发现的，其中两个是以前报道的。3.IRS-1基因多态性在胰岛素抵抗发生中的作用评估：NIDDM组4个IRS-1错义突变的发生率显著高于对照组(23.4%vs.8.5%，P&lt；两个错义突变(M209T和S809F)仅在NIDDM中被发现。NIDDM组和对照组在正常血糖钳夹期间的平衡葡萄糖输注率(GIRS)分别比没有IRS-1多态的相似组分别降低29.5%和22.0%，尽管这可能是由于研究的受试者数量较少，但没有统计学意义。

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.