{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:26:20Z","timestamp":1773077180143,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Association of the major histocompatibility complex (MHC) class II-encoded HLA-DRB1-DQA1-DQB1 haplotype with Graves' disease (GD) has been known for several years. Recent evidence from other autoimmune diseases has suggested that the HLA class I encoded HLA-B\/-C molecules could be conferring HLA-DRB1-DQA1-DQB1 independent effects on disease. The aim of this study was to determine the effect of HLA-B and HLA-C in GD in a white ethnic group of 806 patients with GD and 487 control subjects from the UK. Of the five loci (HLA-B, -C, -DRB1, -DQA1, -DQB1), HLA-C demonstrated the strongest association (P = 1.20 \u00d7 10\u221220) with HLA-C*07 predisposing [OR = 1.63, 95% CI (1.23\u20132.17)] and both HLA-C*03 [OR = 0.54, 95% CI (0.38\u20130.77)], HLA-C*16 [OR = 0.36, 95% CI (0.21\u20130.61)] protective. The other loci were then tested for HLA-C-independent associations. HLA-B was found to be associated independently of HLA-C (P = 1.54 \u00d7 10\u22126) with the other three loci, HLA-DRB1, HLA-DQB1 and HLA-DQA1, also improving the model but with less confidence (P &amp;gt; 10\u22125). This study has for the first time provided evidence of a primary association of HLA-C, and to a lesser extent HLA-B, with GD. Class II loci could still have effects on GD, but they appear smaller than the HLA-C association. A full investigation of the MHC region, including all class I and II loci is now required. Our results point to a primary role for class I-mediated responses in GD, a condition classically assumed to be a straightforward HLA-class II-restricted autoantibody response to the thyroid stimulating hormone receptor.<\/jats:p>","DOI":"10.1093\/hmg\/ddm165","type":"journal-article","created":{"date-parts":[[2007,6,28]],"date-time":"2007-06-28T05:02:08Z","timestamp":1183006928000},"page":"2149-2153","source":"Crossref","is-referenced-by-count":70,"title":["A novel and major association of<i>HLA-C<\/i>in Graves' disease that eclipses the classical<i>HLA-DRB1<\/i>effect"],"prefix":"10.1093","volume":"16","author":[{"given":"Matthew J.","family":"Simmonds","sequence":"first","affiliation":[{"name":"University of Birmingham 1 \u00a0 Division of Medical Sciences, Institute of Biomedical Research , , Birmingham B15 2TT , UK and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna M.M.","family":"Howson","sequence":"additional","affiliation":[{"name":"University of Cambridge 2 \u00a0 Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research , , Cambridge CB2 0XY , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne M.","family":"Heward","sequence":"additional","affiliation":[{"name":"University of Birmingham 1 \u00a0 Division of Medical Sciences, Institute of Biomedical Research , , Birmingham B15 2TT , UK and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackie","family":"Carr-Smith","sequence":"additional","affiliation":[{"name":"University of Birmingham 1 \u00a0 Division of Medical Sciences, Institute of Biomedical Research , , Birmingham B15 2TT , UK and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayne A.","family":"Franklyn","sequence":"additional","affiliation":[{"name":"University of Birmingham 1 \u00a0 Division of Medical Sciences, Institute of Biomedical Research , , Birmingham B15 2TT , UK and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Todd","sequence":"additional","affiliation":[{"name":"University of Cambridge 2 \u00a0 Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research , , Cambridge CB2 0XY , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.L.","family":"Gough","sequence":"additional","affiliation":[{"name":"University of Birmingham 1 \u00a0 Division of Medical Sciences, Institute of Biomedical Research , , Birmingham B15 2TT , UK and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,6,27]]},"reference":[{"key":"2023080909584284200_DDM165C1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/bmb\/ldh032","article-title":"Genetic insights into disease mechanisms of autoimmunity","volume":"71","author":"Simmonds","year":"2004","journal-title":"Br. 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