PT - JOURNAL ARTICLE AU - Lempainen, Johanna AU - Hermann, Robert AU - Veijola, Riitta AU - Simell, Olli AU - Knip, Mikael AU - Ilonen, Jorma TI - Effect of the <em>PTPN22</em> and <em>INS</em> Risk Genotypes on the Progression to Clinical Type 1 Diabetes After the Initiation of β-Cell Autoimmunity AID - 10.2337/db11-0386 DP - 2012 Apr 01 TA - Diabetes PG - 963--966 VI - 61 IP - 4 4099 - http://diabetes.diabetesjournals.org/content/61/4/963.short 4100 - http://diabetes.diabetesjournals.org/content/61/4/963.full SO - Diabetes2012 Apr 01; 61 AB - We set out to analyze the role of two major non-HLA gene polymorphisms associated with type 1 diabetes (T1D), PTPN22 1858C/T and insulin gene INS−23 A/T in progression to clinical T1D after the appearance of β-cell autoimmunity. The study population comprised 249 children with HLA-associated T1D susceptibility. All subjects were persistently positive for at least one of the T1D-associated biochemically defined autoantibodies (insulin autoantibody, GAD antibody, or IA-2 antibody), and 136 subjects presented with T1D over a median follow-up of 4.3 years (range 0.0–12.5) after the appearance of the first autoantibody. The PTPN22 1858T allele was strongly associated with progression to T1D after the appearance of the first biochemically defined β-cell autoantibody (hazard ratio 1.68 [95% CI 1.09–2.60], P = 0.02 Cox regression analysis, multivariate test), and the effect remained similar when analyzed after the appearance of the second autoantibody (P = 0.013), whereas INS−23 HphI AA genotype was not associated with progression to clinical diabetes after the appearance of the first or second autoantibody (P = 0.38 and P = 0.88, respectively). The effect of the INS risk genotype seems to be limited to the induction and early phases of β-cell autoimmunity, but the PTPN22 1858T allele instead affects the initiation and late progression phase of diabetes-associated autoimmunity.