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

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

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Abstract

Aims/hypothesis: The 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. Methods: The 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. Results: In 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/interpretation: This 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.

Original languageEnglish
Pages (from-to)98-102
Number of pages5
JournalDiabetologia
Volume53
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

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Keywords

  • Genetic susceptibility
  • IFIH1
  • Meta-analysis
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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