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.

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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Subjects

Authors

Publication date

2010-01-21

Journal

Diabetologia
Diabetologia (1432-0428)

Journal topics

Language

Eng.

Copyright

CellScreen Applied Biomedical Research Center, Semmelweis University, Budapest, Hungary. jermendy [at] gmail.com

Release reference

Diabetologia. 2010 Jan;53(1):98-102