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The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with type 1 diabetes in both the high-incidence Finnish and the medium-incidence Hungarian populations |
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| Authors: | A Jermendy I Szatmári A P Laine K Lukács K H Horváth A Körner L Madácsy R Veijola O Simell M Knip J Ilonen R Hermann |
| Institution: | 1. CellScreen Applied Biomedical Research Center, Semmelweis University, Budapest, Hungary 2. 1st Department of Paediatrics, Semmelweis University, Bókay u 53-54, 1083, Budapest, Hungary 3. Immunogenetics Laboratory, Medicity Research Laboratories, University of Turku, Turku, Finland 4. Department of Paediatrics, University of Oulu, Oulu, Finland 5. Department of Paediatrics, University of Turku, Turku, Finland 6. Department of Paediatrics, Tampere University Hospital, Tampere, Finland 7. Hospital for Children and Adolescents and Folkh?lsan Research Center, University of Helsinki, Helsinki, Finland 8. Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland |
| Abstract: | Aims/hypothesisThe rs1990760 polymorphism (Ala946Thr) of interferon induced with helicase C domain 1 (IFIH1) has been proposed to associate with type 1 diabetes. In this study, association between IFIH1 Ala946Thr and type 1 diabetes was investigated in two distinct white populations, the Hungarians and Finns.MethodsThe rs1990760 polymorphism was genotyped in 757/509 Hungarian/Finnish childhood-onset cases, 499/250 Hungarian/Finnish control individuals and in 529/924 Hungarian/Finnish nuclear family trios. Disease association was tested using case–control and family-based approaches. A meta-analysis of data from 9,546 cases and 11,000 controls was also performed.ResultsIn the Hungarian dataset, the A allele was significantly more frequent among cases than among controls (OR 1.29, 95% CI 1.10–1.52; p?=?0.002). Combined analysis of Hungarian and Finnish datasets revealed a strong disease association (OR 1.235, 95% CI 1.083–1.408; p?=?0.002). Furthermore, the A allele was significantly overtransmitted in both family trio datasets (p?=?0.017 in Hungarians; p?=?0.007 in Finns). The A allele was increased in Hungarian vs Finnish cases (64.9% vs 60.8% in Finns; p?=?0.003). The meta-analysis yielded a significant effect for IFIH1 rs1990760 A allele on type 1 diabetes risk (OR 1.176, 95% CI 1.130–1.225; p?=?5.3?×?10?15) with significant heterogeneity between effect sizes across the studied populations (p?=?0.023).Conclusions/interpretationThis study represents the first independent confirmation of the association between type 1 diabetes and the IFIH1 gene in Hungarian and Finnish populations. Summarising the data published so far, a clear association between the Ala946Thr polymorphism and type 1 diabetes was detected, with an apparent difference in the contribution to disease susceptibility in different populations of European ancestry. |
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