title: 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 ± 0.47 ng/ml versus 1.12 ± 0.45 ng/ml, P = 0.0065) and healthy controls (AA/AA versus GT/GT: 0.67 ± 0.28 ng/ml versus 0.51 ± 0.33 ng/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.
authors.affiliation: Department of Molecular Diagnostics, National Research Center GosNIIgenetika, Moscow, Russia. dimitry.chistiakov@lycos.com
authors.forename: D A
authors.initials: DA
authors.lastname: Chistiakov
authors.forename: E I
authors.initials: EI
authors.lastname: Chistiakova
authors.forename: N V
authors.initials: NV
authors.lastname: Voronova
authors.forename: R I
authors.initials: RI
authors.lastname: Turakulov
authors.forename: K V
authors.initials: KV
authors.lastname: Savost'anov
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011110:Polymorphism, Genetic; D012426:Russia
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit