A Variant of the Il2ra/Cd25 Gene Predisposing to Graves' Disease is Associated with Increased Levels of Soluble Interleukin-2 Receptor

Abstract

Alpha-subunit of the IL-2 receptor (IL-2Rα) encoded by the IL2RA/CD25 gene binds IL-2 that plays a pivotal role in the regulation of T cell function. Levels of a soluble form of IL-2Rα (sIL-2Rα) lacking the transmembrane and cytoplasmic domains were shown to be increased in several autoimmune diseases including Graves' disease (GD). Recent studies showed association between the IL2RA/CD25 gene variants and several autoimmune diseases including GD. In this study, we analyzed whether polymorphic markers rs2104286, rs41295061, and rs11594656 located at the IL2RA/CD25 locus confer susceptibility to GD and are related to increased concentrations of sIL-2Rα. A total of 1474 Russian GD patients and 1609 control subjects were genotyped for rs2104286, rs41295061, and rs11594656 using a Taqman assay. Concentrations of sIL-2Rα in sera of affected and non-affected individuals were measured using an ELISA test. A minor allele A of rs41295061 showed significant association with increased risk of GD [odds ratio (OR)=1.43, P c=0.00102]. The allele A of rs41295061 and allele A of rs11594656 constitute a higher risk haplotype AA (OR=1.47, P c=0.0477). Compared to carriers of the protective haplogenotype GT/GT, the carriage of two copies of the haplogenotype AA/AA was associated with elevated levels of sIL-2Rα in both GD patients (AA/AA versus GT/GT: 1.35±0.47ng/ml versus 1.12±0.45ng/ml, P=0.0065) and healthy controls (AA/AA versus GT/GT: 0.67±0.28ng/ml versus 0.51±0.33ng/ml, P=0.0098). This is the first report presenting correlation between the carriage of disease-associated variants of IL2RA/CD25 with increased levels of sIL-2Rα in GD. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.