title: The Gly972-->Arg IRS-1 variant is associated with type 1 diabetes in continental Italy.
abstract: The Arg(972) insulin receptor substrate-1 (IRS-1) variant has been hypothesized to play a role in pancreatic beta-cell stimulus-coupled insulin secretion and survival. We analyzed the relations between type 1 diabetes and the Arg(972) IRS-1 variant. The frequency of the IRS-1 Arg(972) variant was investigated in two independent sets of unrelated patients: a case-control study and a collection of type 1 diabetes simplex families. In the former group, frequency of the IRS-1 Arg(972) variant was significantly increased in the patients (P = 0.0008), conferring an OR of 2.5. Transmission disequilibrium analysis of data obtained from the family set revealed that the Arg(972) IRS-1 variant was transmitted from heterozygous parents to affected probands at a frequency of 70.2% (P < 0.02). Arg(972) IRS-1 frequency showed no significant correlation with HLA genotypic risk for type 1 diabetes. Arg(972) IRS-1 type 1 diabetic patients also had lower fasting plasma concentrations of C-peptide at the time of diagnosis with respect to patients carrying the wild-type IRS-1 (0.49 +/- 0.058, n = 34, and 0.76 +/- 0.066, n = 134, respectively [means +/- SE]; P = 0.051). Our findings suggest a role for Arg(972) IRS-1 in conferring risk for the development of type 1 diabetes.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, via Montpellier 1, 56100 Rome, Italy. federicm@uniroma2.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.forename: Antonio
authors.initials: A
authors.lastname: Petrone
authors.forename: Ottavia
authors.initials: O
authors.lastname: Porzio
authors.forename: Carla
authors.initials: C
authors.lastname: Bizzarri
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Rossella
authors.initials: R
authors.lastname: D'Alfonso
authors.forename: Ippolita
authors.initials: I
authors.lastname: Patera
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
authors.forename: Lorenza
authors.initials: L
authors.lastname: Nisticò
authors.forename: Marco
authors.initials: M
authors.lastname: Baroni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
authors.forename: Umberto
authors.initials: U
authors.lastname: di Mario
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
mesh_terms: D000293:Adolescent; D000328:Adult; D001120:Arginine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006801:Humans; D007223:Infant; D055504:Insulin Receptor Substrate Proteins; D007558:Italy; D008297:Male; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D001120:Arginine