Skip to main content
Top
Published in: Diabetologia 1/2010

01-01-2010 | Short Communication

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

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, The Finnish Paediatric Diabetes Registry, The HUNT1DGENES Programme

Published in: Diabetologia | Issue 1/2010

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Knip M, Veijola R, Virtanen SM, Hyoty H, Vaarala O, Akerblom HK (2005) Environmental triggers and determinants of type 1 diabetes. Diabetes 54(Suppl 2):S125–S136CrossRefPubMed Knip M, Veijola R, Virtanen SM, Hyoty H, Vaarala O, Akerblom HK (2005) Environmental triggers and determinants of type 1 diabetes. Diabetes 54(Suppl 2):S125–S136CrossRefPubMed
2.
go back to reference Smyth DJ, Cooper JD, Bailey R et al (2006) A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet 38:617–619CrossRefPubMed Smyth DJ, Cooper JD, Bailey R et al (2006) A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet 38:617–619CrossRefPubMed
3.
go back to reference Hermann R, Bartsocas CS, Soltesz G et al (2004) Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA Class II alleles as disease markers. A comparison between three European populations with variable rates of disease incidence. Diabetes Metab Res Rev 20:322–329CrossRefPubMed Hermann R, Bartsocas CS, Soltesz G et al (2004) Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA Class II alleles as disease markers. A comparison between three European populations with variable rates of disease incidence. Diabetes Metab Res Rev 20:322–329CrossRefPubMed
4.
go back to reference DIAMOND Project Group (2006) Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabet Med 23:857–866CrossRef DIAMOND Project Group (2006) Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabet Med 23:857–866CrossRef
5.
go back to reference Viskari H, Ludvigsson J, Uibo R et al (2004) Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project. J Med Virol 72:610–617CrossRefPubMed Viskari H, Ludvigsson J, Uibo R et al (2004) Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project. J Med Virol 72:610–617CrossRefPubMed
6.
go back to reference Liu S, Wang H, Jin Y et al (2009) IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells. Hum Mol Genet 18:358–365CrossRefPubMed Liu S, Wang H, Jin Y et al (2009) IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells. Hum Mol Genet 18:358–365CrossRefPubMed
7.
go back to reference Aminkeng F, Van Autreve JE, Weets I et al (2009) IFIH1 gene polymorphisms in type 1 diabetes: genetic association analysis and genotype–phenotype correlation in the Belgian population. Hum Immunol 70:706–710CrossRefPubMed Aminkeng F, Van Autreve JE, Weets I et al (2009) IFIH1 gene polymorphisms in type 1 diabetes: genetic association analysis and genotype–phenotype correlation in the Belgian population. Hum Immunol 70:706–710CrossRefPubMed
8.
go back to reference Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KGM (2006) Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 6:50CrossRefPubMed Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KGM (2006) Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 6:50CrossRefPubMed
9.
go back to reference Qu HQ, Marchand L, Grabs R, Polychronakos C (2008) The association between the IFIH1 locus and type 1 diabetes. Diabetologia 51:473–475CrossRefPubMed Qu HQ, Marchand L, Grabs R, Polychronakos C (2008) The association between the IFIH1 locus and type 1 diabetes. Diabetologia 51:473–475CrossRefPubMed
10.
go back to reference Nejentsev S, Walker N, Riches D, Egholm M, Todd JA (2009) Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324:387–389CrossRefPubMed Nejentsev S, Walker N, Riches D, Egholm M, Todd JA (2009) Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324:387–389CrossRefPubMed
Metadata
Title
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
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
The Finnish Paediatric Diabetes Registry
The HUNT1DGENES Programme
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 1/2010
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1561-y

Other articles of this Issue 1/2010

Diabetologia 1/2010 Go to the issue

List of Referees

List of referees

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.