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Winkler, C. ; Lauber, C. ; Adler, K.* ; Grallert, H. ; Illig, T. ; Ziegler, A.-G. ; Bonifacio, E.*

An interferon-induced helicase (IFIH1) gene polymorphism associates with different rates of progression from autoimmunity to type 1 diabetes.

Diabetes 60, 685-690 (2011)
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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. RESEARCH DESIGN AND 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Antibody standardization program; Islet autoantibodies; German Babydiab; Children; Risk; Pathogenesis; Appearance; Prediction; Childhood; Infection
Reviewing status
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Research Unit Molecular Epidemiology (AME)
Institute for Pancreatic Beta Cell Research (IPI)