title: Molecular scanning for mutations in the insulin receptor substrate-1 (IRS-1) gene in Turkish with type 2 diabetes mellitus.
abstract: Insulin receptor substrate-1 (IRS-1) is an endogenous substrate for the insulin receptor tyrosine kinase, which plays a key role in insulin signaling. Recent studies have identified several polymorphisms in the human IRS-1 gene (Irs-1) that are increased in prevalence among type 2 diabetic patients. To determine whether variation in the Irs-1 contributes to genetic susceptibility to type 2 diabetes in Turkish people, PCR-RFLP and DNA sequencing method were utilized to analyze the coding region of Irs-1 in 70 subject and 116 control patients. Three missense mutations were detected (Gly972Arg, Ala512Pro, Ser892Gly). There was no significant association found with any of these variants and diabetes. The Gly972Arg mutation, however, was relatively more common in with 10/70 diabetic patients and 15/116 non-diabetic controls being heterozygous and 1/70 being and 0/116 non-diabetic controls being homozygous for this variant. As a conclusion, Ala512Pro, Ser892Gly mutations were rare and Met613Val, Ser1043Tyr and Cys1095Tyr mutations were not found in the populations studied. Gly972Arg is more common than other known mutations in our population but may not be a major determinant in genetic susceptibility to type 2 diabetes.
authors.affiliation: Institute for Molecular & Human Genetics, Georgetown University, Washington, DC 20007, USA.
authors.forename: Funda E
authors.initials: FE
authors.lastname: Orkunoglu Suer
authors.forename: Hatice
authors.initials: H
authors.lastname: Mergen
authors.forename: Erol
authors.initials: E
authors.lastname: Bolu
authors.forename: Metin
authors.initials: M
authors.lastname: Ozata
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins