RT Journal Article
SR Electronic
T1 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
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 963
OP 966
DO 10.2337/db11-0386
VO 61
IS 4
A1 Lempainen, Johanna
A1 Hermann, Robert
A1 Veijola, Riitta
A1 Simell, Olli
A1 Knip, Mikael
A1 Ilonen, Jorma
YR 2012
UL http://diabetes.diabetesjournals.org/content/61/4/963.abstract
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.