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


Correspondence: Magdalena Żurawek, Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, Poznan 60-479, Poland. Tel.: +48 61 657 9281; Fax: +48 61 823 3235; E-mail: zurawek@man.poznan.pl



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).


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.


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, = 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, = 0·04). Both statistically significant differences, for rs1990760 and rs13422767 SNPs, did not survive the Bonferroni correction (= 0·11 and = 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, = 0·56 and OR = 1·08, = 0·50, respectively).


The IFIH1 locus polymorphisms are unlikely to be associated with Addison's disease