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. 2010 Jan;53(1):98-102.
doi: 10.1007/s00125-009-1561-y. Epub 2009 Oct 20.

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  1 , I Szatmári, A P Laine, K Lukács, K H Horváth, A Körner, L Madácsy, R Veijola, O Simell, M Knip, J Ilonen, R Hermann; Finnish Paediatric Diabetes Registry; HUNT1DGENES Programme
Collaborators, Affiliations

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 et al. Diabetologia. 2010 Jan.

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 x 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.

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