Polymorphisms in the interferon‐induced helicase (IFIH1) locus and susceptibility to Addison's disease. (7th January 2013)

• Record Type: Journal Article
• Authors: Żurawek, Magdalena; Fichna, Marta; Januszkiewicz, Danuta; Fichna, Piotr; Nowak, Jerzy
• Is Part Of: Clinical endocrinology. Volume 78:Number 2(2013:Feb.)
• Page Start: 191
• Page End: 196
• Publication Date: 2013-01-07
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/j.1365-2265.2012.04497.x
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen4497-abs-0001"> <title>Abstract</title> <sec id="cen4497-sec-0001" sec-type="section"> <title>Objective</title> <p>The interferon‐induced helicase C domain‐containing protein 1 (<italic>IFIH1</italic>) gene encodes a sensor for double‐stranded RNA that initiates antiviral activity against enteroviruses. Previous investigations have indicated a role for <italic>IFIH1</italic> in autoimmunity, as common and rare polymorphisms in this gene have been associated with type 1 diabetes. We hypothesized that polymorphisms in the <italic>IFIH1</italic> locus may play a role in the pathogenesis of autoimmune Addison's disease (AAD).</p> </sec> <sec id="cen4497-sec-0002" sec-type="section"> <title>Design</title> <p>We analysed the association of rs3747517, rs1990760, rs2111485 and rs13422767 single‐nucleotide polymorphisms (SNPs) in the <italic>IFIH1</italic> 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.</p> </sec> <sec id="cen4497-sec-0003" sec-type="section"> <title>Results</title> <p>The major AA genotype of the coding SNP rs1990760 appeared significantly more frequently in AAD compared with healthy individuals (AG <italic>vs </italic>AA OR 0·62, 95%CI 0·40–0·95, <italic>P </italic>= 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 <italic>vs</italic> G OR 0·65, 95%CI 0·43–0·98, <italic>P </italic>= 0·04). Both statistically significant differences, for rs1990760 and rs13422767 SNPs, did not survive the Bonferroni correction (<italic>P </italic>= 0·11 and <italic>P </italic>= 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<italic> </italic>= 1·05, <italic>P </italic>= 0·56 and OR<italic> </italic>= 1·08, <italic>P </italic>= 0·50, respectively).</p> </sec> <sec id="cen4497-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The IFIH1 locus polymorphisms are unlikely to be associated with Addison's disease</p> </sec> </abstract>