The Gly972 → Arg IRS-1 variant is associated with type 1 diabetes in continental Italy

Massimo Federici, Antonio Petrone, Ottavia Porzio, Carla Bizzarri, Davide Lauro, Rossella D'Alfonso, Ippolita Patera, Marco Cappa, Lorenza Nisticò, Marco Baroni, Giorgio Sesti, Umberto Di Mario, Renato Lauro, Raffaella Buzzetti

Research output: Contribution to journalArticlepeer-review


The Arg972 insulin receptor substrate-1 (IRS-1) variant has been hypothesized to play a role in pancreatic β-cell stimulus-coupled insulin secretion and survival. We analyzed the relations between type 1 diabetes and the Arg972 IRS-1 variant. The frequency of the IRS-1 Arg972 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 Arg972 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 Arg972 IRS-1 variant was transmitted from heterozygous parents to affected probands at a frequency of 70.2% (P <0.02). Arg972 IRS-1 frequency showed no significant correlation with HLA genotypic risk for type 1 diabetes. Arg972 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 Arg972 IRS-1 in conferring risk for the development of type 1 diabetes.

Original languageEnglish
Pages (from-to)887-890
Number of pages4
Issue number3
Publication statusPublished - Mar 1 2003


  • IRS-I, insulin receptor substrate-1
  • P13, phosphatidylinositol-3
  • PPV, positive predictive value
  • TDT, transmission disequilibrium test

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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