【摘要】 为了探讨胰岛素受体底物 2 (insulinreceptorsubstrate 2 ,简称IRS 2 )基因 3′ 非翻译区 (3′ untranslatedregion,简称 3′ UTR)的分子变异及其与 2型糖尿病 (type 2diabetesmellitus,简称T2DM)的关系 ,从湖南地区 12 8例T2DM患者外周血白细胞中提取基因组DNA ,采用聚合酶链式反应 (polymerasechainreaction ,简称PCR) 变性高效液相色谱 (denatur inghigh performanceliquidchromatography,简称DHPLC)技术筛查IRS 2基因 3′ UTR ,对DHPLC峰型异常样品进行序列分析。在 18例T2DM患者IRS 2基因 3′ UTR的 4 0 6 4bp处发现T→C的突变。IRS 2基因 3′ UTR的T40 64→C突变可能与T2DM有关。更多还原

【Abstract】 Insulin receptor substrate-2(IRS-2) belongs to a family of cytoplasmic adaptor proteins,which link insulin,insulin-like growth factor-1(IGF-1),and cytokine receptor tyrosine kinases to signaling pathways regulating metabolism,growth,differentiation,reproduction,and homestasis.Deficiency of IRS-2 in mice causes type 2 diabetes mellitus (T2DM),suggesting that abnormal structure and dysfunction of the IRS-2 gene may contribute to the pathogenesis of T2DM.Variations in the open reading frame (ORF) and promoter region of IRS-2 gene in patients with T2DM have been reported over the past few years.These genetic variations are from ethnically different patients,confounding any analysis of the contribution of IRS-2 gene variations to the development of T2DM.The 3′-untranslated region(3′-UTR)of IRS-2 gene variation may be contribute to the T2DM.So far,the relationship between 3′-UTR of IRS-2 gene variations and T2DM have not been investigated.Based on the 3′-UTR of eukaryotic gene plays an important role in the eukaryotic gene regulation,we investigated abnormalities of IRS-2 gene 3′-UTR and their relation with T2DM in the Chinese population.Genomic DNA was extracted from leukocyte of 128 patients with T2DM and 125 control subjects in Hunan,China.A segment of IRS-2 gene 3′-UTR was scanned by polymerase chain reaction(PCR)-denaturing high-performance liquid chromatography (DHPLC).All PCR products with abnormal DHPLC pattern were submitted to DNA sequence analysis.A T→C mutation at 4064 bp of IRS-2 gene 3′-UTR was found in 18 patients with T2DM ,while it was only found in 5 control subjects.The incidence of the mutation in patients with T2DM were much higher than that in contol subjects (14.1% vs 4.0%,x 2=7.748,P=0.005).These results indicate that the T_ 4064 →C in IRS-2 gene 3′-UTR may be related to Chinese patients with T2DM.更多还原