A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect.
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 HL...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1826300366412578816 |
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| author | Simmonds, M Howson, J Heward, J Carr-Smith, J Franklyn, J Todd, J Gough, S |
| author_facet | Simmonds, M Howson, J Heward, J Carr-Smith, J Franklyn, J Todd, J Gough, S |
| author_sort | Simmonds, M |
| collection | OXFORD |
| description | 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 x 10(-20)) with HLA-C*07 predisposing [OR = 1.63, 95% CI (1.23-2.17)] and both HLA-C*03 [OR = 0.54, 95% CI (0.38-0.77)], HLA-C*16 [OR = 0.36, 95% CI (0.21-0.61)] 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 x 10(-6)) with the other three loci, HLA-DRB1, HLA-DQB1 and HLA-DQA1, also improving the model but with less confidence (P > 10(-5)). 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. |
| first_indexed | 2024-03-07T05:16:04Z |
| format | Journal article |
| id | oxford-uuid:dd3b0457-aa2b-4cf6-80fe-3b2ca2bf504a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:16:04Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:dd3b0457-aa2b-4cf6-80fe-3b2ca2bf504a2022-03-27T09:23:35ZA novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dd3b0457-aa2b-4cf6-80fe-3b2ca2bf504aEnglishSymplectic Elements at Oxford2007Simmonds, MHowson, JHeward, JCarr-Smith, JFranklyn, JTodd, JGough, SAssociation 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 x 10(-20)) with HLA-C*07 predisposing [OR = 1.63, 95% CI (1.23-2.17)] and both HLA-C*03 [OR = 0.54, 95% CI (0.38-0.77)], HLA-C*16 [OR = 0.36, 95% CI (0.21-0.61)] 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 x 10(-6)) with the other three loci, HLA-DRB1, HLA-DQB1 and HLA-DQA1, also improving the model but with less confidence (P > 10(-5)). 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. |
| spellingShingle | Simmonds, M Howson, J Heward, J Carr-Smith, J Franklyn, J Todd, J Gough, S A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect. |
| title | A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect. |
| title_full | A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect. |
| title_fullStr | A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect. |
| title_full_unstemmed | A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect. |
| title_short | A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect. |
| title_sort | novel and major association of hla c in graves disease that eclipses the classical hla drb1 effect |
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