Human Molecular Genetics Advance Access originally published online on June 27, 2007
Human Molecular Genetics 2007 16(18):2149-2153; doi:10.1093/hmg/ddm165
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect
1 Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK and 2 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK
* To whom correspondence should be addressed. Tel: +44 1214158819; Fax: +44 1214158712; Email: s.c.gough{at}bham.ac.uk
Received April 27, 2007; Accepted June 22, 2007
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. K. Huber, E. M. Jacobson, K. Jazdzewski, E. S. Concepcion, and Y. Tomer Interleukin (IL)-23 Receptor Is a Major Susceptibility Gene for Graves' Ophthalmopathy: The IL-23/T-helper 17 Axis Extends to Thyroid Autoimmunity J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 1077 - 1081. [Abstract] [Full Text] [PDF]
|
|