An Interferon-Induced Helicase (IFIH1) Gene Polymorphism Associates With Different Rates of Progression From Autoimmunity to Type 1 Diabetes
- Christiane Winkler1,
- Claudia Lauber1,
- Kerstin Adler2,
- Harald Grallert3,
- Thomas Illig3,
- Anette-Gabriele Ziegler1,2,4 and
- Ezio Bonifacio5
- 1Forschergruppe Diabetes e.V. at Helmholtz Center Munich, Neuherberg, Germany
- 2Forschergruppe Diabetes, Munich University of Technology, Munich, Germany
- 3Institute of Epidemiology, Helmholtz Center Munich, Neuherberg, Germany
- 4Institute of Diabetes Research, Helmholtz Center Munich, Neuherberg, Germany
- 5Center for Regenerative Therapies, Dresden University of Technology, Dresden, Germany
- Corresponding author: Ezio Bonifacio, .
A.-G.Z. and E.B. share senior authorship.
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.
- Received September 9, 2010.
- Accepted November 18, 2010.
- © 2011 by the American Diabetes Association.
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