An Interferon-Induced Helicase (IFIH1) Gene Polymorphism Associates With Different Rates of Progression From Autoimmunity to Type 1 Diabetes
Open accessAbstract
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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Genetic susceptibility might also influence responses to environmental stimuli or physiological pathways.
“Genetic susceptibility might also influence responses to environmental stimuli or physiological pathways (eg, vitamin D and interferon induced helicase).29,76”
From Type 1 diabetes (2014) · cites this paper as [76]
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Self-citation
- Authors
- Winkler, C., Lauber, C., Adler, K., Grallert, H., Illig, T., Ziegler, A.-G., & Bonifacio, E.
- Affiliations
- Helmholtz Munich (DE)
- Technical University of Munich (DE)
- Center for Regenerative Therapies Dresden (DE)
- Corresponding author
- Bonifacio, Ezio
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2011-01-21
- Volume
- 60
- Issue
- 2
- Pages
- 685-690
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3028371
- OpenAlex
- W2101487576
- Cited by
- 68
- References
- 4
- Citations by year
- 2023: 5 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 12
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- MDA5, type 1 diabetes, autoimmunity, disease progression, islet autoantibodies, single nucleotide polymorphisms, genetic susceptibility, PTPN22, HER3, CD25, thyroid peroxidase antibodies, anti-tissue transglutaminase antibodies
- MeSH terms
- Interferon-Induced Helicase, IFIH1, Adolescent, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Enzyme-Linked Immunosorbent Assay, Female, Genotype, Humans, Infant, Islets of Langerhans, Male, Prospective Studies, Autoimmunity, Disease Progression, Polymorphism, Single Nucleotide, DEAD-box RNA Helicases, Young Adult, Genetic Association Studies
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