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Polymorphisms in the interferon‐induced helicase ( IFIH 1 ) locus and susceptibility to A ddison's disease
Author(s) -
Żurawek Magdalena,
Fichna Marta,
Januszkiewicz Danuta,
Fichna Piotr,
Nowak Jerzy
Publication year - 2013
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2012.04497.x
Subject(s) - genotyping , single nucleotide polymorphism , genotype , allele , snp , locus (genetics) , biology , pathogenesis , autoimmunity , gene , microbiology and biotechnology , genetics , immunology , antibody
Objective The interferon‐induced helicase C domain‐containing protein 1 ( IFIH1 ) gene encodes a sensor for double‐stranded RNA that initiates antiviral activity against enteroviruses. Previous investigations have indicated a role for IFIH1 in autoimmunity, as common and rare polymorphisms in this gene have been associated with type 1 diabetes. We hypothesized that polymorphisms in the IFIH1 locus may play a role in the pathogenesis of autoimmune Addison's disease ( AAD ). Design We analysed the association of rs3747517, rs1990760, rs2111485 and rs13422767 single‐nucleotide polymorphisms ( SNP s) in the IFIH1 gene and intergenic region with AAD in a Polish cohort. The study comprised 120 patients with AAD and 689 healthy control individuals. Genotyping was performed using T aq M an genotyping assays. Results The major AA genotype of the coding SNP rs1990760 appeared significantly more frequently in AAD compared with healthy individuals ( AG vs AA OR 0·62, 95% CI 0·40–0·95, P = 0·03). We also observed a significant difference in the distribution of the rs13422767 SNP alleles. The major G allele was more frequent in the AAD group (A vs G OR 0·65, 95% CI 0·43–0·98, P = 0·04). Both statistically significant differences, for rs1990760 and rs13422767 SNP s, did not survive the B onferroni correction ( P = 0·11 and P = 0·15, for AA genotype and G allele, respectively). Subsequently, a meta‐analysis of 519 patients with AAD and 1362 controls from three different European populations was performed. Under a fixed‐effect model, a pooled OR for A allele and AA genotype of rs1990760 did not display any significant increase among AAD ( OR = 1·05, P = 0·56 and OR = 1·08, P = 0·50, respectively). Conclusion The IFIH1 locus polymorphisms are unlikely to be associated with Addison's disease