A Variant of the Il2ra / Cd25 Gene Predisposing to Graves’ Disease is Associated with Increased Levels of Soluble Interleukin‐2 Receptor
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 diseas...
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| Veröffentlicht in: | Scandinavian journal of immunology 2011-11, Vol.74 (5), p.496-501 |
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| creator | Chistiakov, D. A. Chistiakova, E. I. Voronova, N. V. Turakulov, R. I. Savost’anov, K. V. |
| description | 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, Pc = 0.00102]. The allele A of rs41295061 and allele A of rs11594656 constitute a higher risk haplotype AA (OR = 1.47, Pc = 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. |
| doi_str_mv | 10.1111/j.1365-3083.2011.02608.x |
| format | Article |
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A. ; Chistiakova, E. I. ; Voronova, N. V. ; Turakulov, R. I. ; Savost’anov, K. V.</creator><creatorcontrib>Chistiakov, D. A. ; Chistiakova, E. I. ; Voronova, N. V. ; Turakulov, R. I. ; Savost’anov, K. V.</creatorcontrib><description>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, Pc = 0.00102]. The allele A of rs41295061 and allele A of rs11594656 constitute a higher risk haplotype AA (OR = 1.47, Pc = 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.</description><identifier>ISSN: 0300-9475</identifier><identifier>EISSN: 1365-3083</identifier><identifier>DOI: 10.1111/j.1365-3083.2011.02608.x</identifier><identifier>PMID: 21815908</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Autoimmune diseases ; Case-Control Studies ; CD25 antigen ; DNA Mutational Analysis ; Enzyme-linked immunosorbent assay ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Graves Disease - blood ; Graves Disease - epidemiology ; Graves Disease - genetics ; Graves Disease - immunology ; Graves' disease ; Haplotypes ; Humans ; Interleukin 2 ; Interleukin 2 receptors ; Interleukin-2 Receptor alpha Subunit - genetics ; Interleukin-2 Receptor alpha Subunit - immunology ; Interleukin-2 Receptor alpha Subunit - metabolism ; Lymphocytes T ; Male ; Polymorphism, Genetic ; Risk factors ; Russia</subject><ispartof>Scandinavian journal of immunology, 2011-11, Vol.74 (5), p.496-501</ispartof><rights>2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd</rights><rights>2011 The Authors. 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A.</creatorcontrib><creatorcontrib>Chistiakova, E. I.</creatorcontrib><creatorcontrib>Voronova, N. V.</creatorcontrib><creatorcontrib>Turakulov, R. I.</creatorcontrib><creatorcontrib>Savost’anov, K. V.</creatorcontrib><title>A Variant of the Il2ra / Cd25 Gene Predisposing to Graves’ Disease is Associated with Increased Levels of Soluble Interleukin‐2 Receptor</title><title>Scandinavian journal of immunology</title><addtitle>Scand J Immunol</addtitle><description>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, Pc = 0.00102]. The allele A of rs41295061 and allele A of rs11594656 constitute a higher risk haplotype AA (OR = 1.47, Pc = 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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Autoimmune diseases</subject><subject>Case-Control Studies</subject><subject>CD25 antigen</subject><subject>DNA Mutational Analysis</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Graves Disease - blood</subject><subject>Graves Disease - epidemiology</subject><subject>Graves Disease - genetics</subject><subject>Graves Disease - immunology</subject><subject>Graves' disease</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Interleukin 2</subject><subject>Interleukin 2 receptors</subject><subject>Interleukin-2 Receptor alpha Subunit - genetics</subject><subject>Interleukin-2 Receptor alpha Subunit - immunology</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Polymorphism, Genetic</subject><subject>Risk factors</subject><subject>Russia</subject><issn>0300-9475</issn><issn>1365-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcuO0zAUhi0EYsrAKyDvWCXjS3xbsKjKUIoqgRhgaznJCePiJsVO5rLrmtVseb0-CQkdZgtHss6Rzn_-X_KHEKYkp2OdbXLKpcg40TxnhNKcMEl0fvMIzR4Wj9GMcEIyUyhxgp6ltCGEcqb4U3TCqKbCED1Dd3P81UXv2h53De4vAa8Ci-6w_3k2vkXNBF5CC_hjhNqnXZd8-w33HV5GdwXpsP-F3_gELgH2Cc9T6irveqjxte8v8aqt4rSr8RquIKQp4qILQxnGmLaHGGD47tvD_o7hT1DBru_ic_SkcSHBi_t-ir68Pf-8eJetPyxXi_k6qwpBdAZclUxSIR3TtTCi0k4VxtBGlqyBsjAFKVRdS-fKwjFFKa8c15KpxlEoteGn6NXRdxe7HwOk3m59qiAE10I3JGvGfxaUc_VPpTZSM6nI5KmPyip2KUVo7C76rYu3lhI7gbMbO_GxEx87gbN_wNmb8fTlfchQbqF-OPxLahS8PgqufYDb_za2F-9X08R_A3VZqeU</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Chistiakov, D. A.</creator><creator>Chistiakova, E. I.</creator><creator>Voronova, N. V.</creator><creator>Turakulov, R. I.</creator><creator>Savost’anov, K. V.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201111</creationdate><title>A Variant of the Il2ra / Cd25 Gene Predisposing to Graves’ Disease is Associated with Increased Levels of Soluble Interleukin‐2 Receptor</title><author>Chistiakov, D. A. ; Chistiakova, E. I. ; Voronova, N. V. ; Turakulov, R. I. ; Savost’anov, K. 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A.</creatorcontrib><creatorcontrib>Chistiakova, E. I.</creatorcontrib><creatorcontrib>Voronova, N. V.</creatorcontrib><creatorcontrib>Turakulov, R. I.</creatorcontrib><creatorcontrib>Savost’anov, K. V.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Scandinavian journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chistiakov, D. A.</au><au>Chistiakova, E. I.</au><au>Voronova, N. V.</au><au>Turakulov, R. I.</au><au>Savost’anov, K. V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Variant of the Il2ra / Cd25 Gene Predisposing to Graves’ Disease is Associated with Increased Levels of Soluble Interleukin‐2 Receptor</atitle><jtitle>Scandinavian journal of immunology</jtitle><addtitle>Scand J Immunol</addtitle><date>2011-11</date><risdate>2011</risdate><volume>74</volume><issue>5</issue><spage>496</spage><epage>501</epage><pages>496-501</pages><issn>0300-9475</issn><eissn>1365-3083</eissn><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, Pc = 0.00102]. The allele A of rs41295061 and allele A of rs11594656 constitute a higher risk haplotype AA (OR = 1.47, Pc = 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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21815908</pmid><doi>10.1111/j.1365-3083.2011.02608.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Autoimmune diseases Case-Control Studies CD25 antigen DNA Mutational Analysis Enzyme-linked immunosorbent assay Female Gene Frequency Genetic Association Studies Genetic Predisposition to Disease Genotype Graves Disease - blood Graves Disease - epidemiology Graves Disease - genetics Graves Disease - immunology Graves' disease Haplotypes Humans Interleukin 2 Interleukin 2 receptors Interleukin-2 Receptor alpha Subunit - genetics Interleukin-2 Receptor alpha Subunit - immunology Interleukin-2 Receptor alpha Subunit - metabolism Lymphocytes T Male Polymorphism, Genetic Risk factors Russia |
| title | A Variant of the Il2ra / Cd25 Gene Predisposing to Graves’ Disease is Associated with Increased Levels of Soluble Interleukin‐2 Receptor |
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