Polymorphisms in the interferon-induced helicase (IFIH1) locus and susceptibility to Addison's disease.

Abstract

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 (SNPs) 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 TaqMan 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 SNPs, did not survive the Bonferroni 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.

• Authors: Magdalena Zurawek, Marta Fichna, Danuta Januszkiewicz, Piotr Fichna, Jerzy Nowak
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 78 Issue 2 Pg. 191-6 (Feb 2013) ISSN: 1365-2265 [Electronic] England
• PMID: 22789000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• IFIH1 protein, human
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1

Topics

• Addison Disease (genetics)
• Adult
• DEAD-box RNA Helicases (genetics, metabolism)
• Female
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interferon-Induced Helicase, IFIH1
• Male
• Middle Aged
• Polymorphism, Genetic
• Young Adult