title: An interferon-induced helicase (IFIH1) gene polymorphism associates with different rates of progression from autoimmunity to type 1 diabetes.
abstract: OBJECTIVE
  Genome-wide association studies have identified gene regions associated with the development of type 1 diabetes. The aim of this study was to determine whether these associations are with the development of autoimmunity and/or progression to diabetes.
  
  
  METHODS
  Children (n = 1,650) of parents with type 1 diabetes were prospectively followed from birth (median follow-up 10.20 years) for the development of islet autoantibodies, thyroid peroxidase antibodies, tissue transglutaminase antibodies, and diabetes. Genotyping for single-nucleotide polymorphisms of the PTPN22, ERBB3, PTPN2, KIAA0350, CD25, and IFIH1 genes was performed using the MassARRAY system with iPLEX chemistry.
  
  
  RESULTS
  Islet autoantibodies developed in 137 children and diabetes developed in 47 children. Type 1 diabetes risk was associated with the IFIH1 rs2111485 single-nucleotide polymorphism (hazard ratio 2.08; 95% CI 1.16-3.74; P = 0.014). None of the other genes were significantly associated with diabetes development in this cohort. IFIH1 genotypes did not associate with the development of islet autoantibodies (P = 0.80) or autoantibodies against thyroid peroxidase (P = 0.55) and tissue transglutaminase (P = 0.66). Islet autoantibody-positive children with the IFIH1 rs2111485 GG genotype had a faster progression to diabetes (31% within 5 years) than children with the type 1 diabetes protective GA or AA genotypes (11% within 5 years; P = 0.006).
  
  
  CONCLUSIONS
  The findings indicate that IFIH1 genotypes influence progression from autoimmunity to diabetes development, consistent with the notion that protective genotypes downregulate responses to environmental insults after initiation of autoimmunity.
authors.affiliation: Forschergruppe Diabetes e.V. at Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Winkler
authors.forename: Claudia
authors.initials: C
authors.lastname: Lauber
authors.forename: Kerstin
authors.initials: K
authors.lastname: Adler
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Anette-Gabriele
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D000072640:Interferon-Induced Helicase, IFIH1; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1