HLA-DR/DQ haplotype in rheumatoid arthritis: novel allelic associations in UK Caucasians

OBJECTIVE: To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). METHODS: HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype...

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Bibliographic Details
Published in:	Journal of rheumatology 2002-09, Vol.29 (9), p.1821-1826
Main Authors:	MILICIC, Anita, LEE, Dorothea, BROWN, Matthew A, DARKE, Chris, WORDSWORT, B. Paul
Format:	Article
Language:	eng
Subjects:	Adult Aged Alleles Arthritis, Rheumatoid - ethnology Arthritis, Rheumatoid - genetics Biological and medical sciences Case-Control Studies Chi-Square Distribution Diseases of the osteoarticular system European Continental Ancestry Group - genetics Female Gene Frequency Genetic Predisposition to Disease Haplotypes HLA-DQ Antigens - genetics HLA-DR Antigens - genetics Humans Inflammatory joint diseases Male Medical sciences Middle Aged Odds Ratio Polymerase Chain Reaction Reference Values Sensitivity and Specificity United Kingdom - epidemiology
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Summary:	OBJECTIVE: To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). METHODS: HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. RESULTS: Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB109, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB10103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRbeta molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. CONCLUSION: These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.
ISSN:	0315-162X 1499-2752