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

Milicic, A., Lee, D., Brown, M. A., Darke, C., & Wordsworth, B. P. (2002) HLA-DR/DQ haplotype in rheumatoid arthritis: Novel allelic associations in UK Caucasians. Journal of Rheumatology, 29(9), pp. 1821-1826.

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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 DRβ 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.

Impact and interest:

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25 citations in Web of Science®

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ID Code: 89550
Item Type: Journal Article
Refereed: Yes
Keywords: Association, HLA-DQ, HLA-DR, Rheumatoid arthritis, HLA DQ antigen, HLA DR antigen, allelism, article, Caucasian, controlled study, data analysis, epitope mapping, ethnic group, gene frequency, gene locus, genetic predisposition, HLA typing, human, hypothesis, major clinical study, phenotype, polymerase chain reaction, priority journal, protein motif, statistical significance, United Kingdom, Adult, Aged, Alleles, Arthritis, Rheumatoid, Case-Control Studies, Chi-Square Distribution, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Great Britain, Haplotypes, HLA-DQ Antigens, HLA-DR Antigens, Humans, Male, Middle Aged, Odds Ratio, Reference Values, Sensitivity and Specificity
ISSN: 0315-162X
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2002 Journal of Rheumatology Publishing Co. Ltd.
Deposited On: 27 Oct 2015 02:55
Last Modified: 27 Oct 2015 02:55

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