[Variation of insulin receptor substrate-2 gene 3'-untranslated region in patients with type 2 diabetes mellitus].
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%, x2 = 7.748, P = 0.005). These results indicate that the T4064-->C in IRS-2 gene 3'-UTR may be related to Chinese patients with T2DM.
Zeng
Wei-Min
WM
Department of Biochemistry, Xiangya Medical School, Central South University, Changsha 410078, China. zengwmin@yahoo.com.cn
Chen
Shu-Hua
SH
Xie
Ping
P
Liu
Mei-Lian
ML
Song
Hui-Ping
HP
D024509:3' Flanking Region / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002681:China; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction
C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D004247:DNA