A Variant of the Il2ra/Cd25 Gene Predisposing to Graves&#39; Disease is Associated with Increased Levels of Soluble Interleukin-2 Receptor

Chistiakov, DA; Chistiakova, EI; Voronova, NV; Turakulov, RI; Savost&#39;anov, KV

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

Author(s): Chistiakov, DA; Chistiakova, EI; Voronova, NV; Turakulov, RI; Savost'anov, KV;
Details: Publication Year 2011-11,Volume 74,Issue #5,Page 496-501
Journal Title: SCANDINAVIAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Alpha-subunit of the IL-2 receptor (IL-2R alpha) 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-2R alpha (sIL-2R alpha) 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-2R alpha. 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-2R alpha 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-2R alpha 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-2R alpha in GD.
Publisher: WILEY-BLACKWELL
Keywords: REGULATORY T-CELLS; SINGLE-NUCLEOTIDE POLYMORPHISMS; MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; IL-2 PRODUCTION; SERUM; AUTOIMMUNE; RECEPTOR; HYPERTHYROIDISM; REGION
Publisher's Version: https://doi.org/10.1111/j.1365-3083.2011.02608.x
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Creation Date: 2011-11-01 12:00:00