Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility. Export

@article{Sutherland_et_al07, abstract = {CONTEXT: A recent large-scale analysis of nonsynonymous coding polymorphisms showed strong evidence that an alanine to threonine amino acid change at codon 946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was associated with type 1 diabetes. Previous investigations have also demonstrated that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed cell death (PDCD1) gene was associated with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: We sought to replicate these genetic associations in Graves' disease and autoimmune Addison's disease patient cohorts. PATIENTS AND METHODS: A total of 602 Graves' disease subjects, 214 Addison's disease subjects, and 446 healthy controls were genotyped for the IFIH1 and PDCD1 single-nucleotide polymorphisms using mass spectrometer analysis of primer extension products (Sequenom). RESULTS: The alanine-carrying allele at the IFIH1 codon 946 polymorphism was present in 796 of 1204 (66\%) Graves' disease patient alleles compared with 508 of 892 (57\%) control subject alleles [odds ratio 1.47 (5-95\% confidence interval, 1.23-1.76); P = 1.9 x 10(-5)]. In contrast, there was no association of alleles at this marker in autoimmune Addison's disease. Neither was there evidence for association in either patient cohort at the PD1.3 polymorphism. CONCLUSIONS: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.}, author = {Sutherland, A. and Davies, J. and Owen, C. J. and Vaikkakara, S. and Walker, C. and Cheetham, T. D. and James, R. A. and Perros, P. and Donaldson, P. T. and Cordell, H. J. and Quinton, R. and Pearce, S. H.}, citeulike-article-id = {4505050}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/jc.2007-0173}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17535987}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17535987}, doi = {10.1210/jc.2007-0173}, issn = {0021-972X}, journal = {The Journal of clinical endocrinology and metabolism}, keywords = {association, graves, ifih1}, month = {August}, number = {8}, pages = {3338--3341}, posted-at = {2009-05-12 13:48:12}, priority = {2}, title = {Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility.}, url = {http://dx.doi.org/10.1210/jc.2007-0173}, volume = {92}, year = {2007} }

TY - JOUR ID - Sutherland_et_al07 L3 - citeulike-article-id:4505050 N2 - CONTEXT: A recent large-scale analysis of nonsynonymous coding polymorphisms showed strong evidence that an alanine to threonine amino acid change at codon 946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was associated with type 1 diabetes. Previous investigations have also demonstrated that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed cell death (PDCD1) gene was associated with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: We sought to replicate these genetic associations in Graves' disease and autoimmune Addison's disease patient cohorts. PATIENTS AND METHODS: A total of 602 Graves' disease subjects, 214 Addison's disease subjects, and 446 healthy controls were genotyped for the IFIH1 and PDCD1 single-nucleotide polymorphisms using mass spectrometer analysis of primer extension products (Sequenom). RESULTS: The alanine-carrying allele at the IFIH1 codon 946 polymorphism was present in 796 of 1204 (66%) Graves' disease patient alleles compared with 508 of 892 (57%) control subject alleles [odds ratio 1.47 (5-95% confidence interval, 1.23-1.76); P = 1.9 x 10(-5)]. In contrast, there was no association of alleles at this marker in autoimmune Addison's disease. Neither was there evidence for association in either patient cohort at the PD1.3 polymorphism. CONCLUSIONS: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders. IS - 8 JF - The Journal of clinical endocrinology and metabolism SN - 0021-972X EP - 3341 TI - Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility. VL - 92 SP - 3338 KW - association KW - graves KW - ifih1 AU - Sutherland, A AU - Davies, J AU - Owen, CJ AU - Vaikkakara, S AU - Walker, C AU - Cheetham, TD AU - James, RA AU - Perros, P AU - Donaldson, PT AU - Cordell, HJ AU - Quinton, R AU - Pearce, SH PY - 2007/08// UR - http://dx.doi.org/10.1210/jc.2007-0173 ER -