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.
OBJECTIVE
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
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.
Jermendy
A
A
CellScreen Applied Biomedical Research Center, Semmelweis University, Budapest, Hungary. jermendy@gmail.com
Szatmári
I
I
Laine
A P
AP
Lukács
K
K
Horváth
K H
KH
Körner
A
A
Madácsy
L
L
Veijola
R
R
Simell
O
O
Knip
M
M
Ilonen
J
J
Hermann
R
R
D017668:Age of Onset; D000409:Alanine; D019943:Amino Acid Substitution; D002648:Child; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005060:Europe; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D000072640:Interferon-Induced Helicase, IFIH1; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D013912:Threonine
D013912:Threonine; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D000409:Alanine