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 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-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 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.


CONCLUSIONS
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.
Milicic
Anita
A
Wellcome Trust Centre for Human Genetics, University of Oxford, UK. anitam@well.ox.ac.uk
Lee
Dorothea
D
Brown
Matthew A
MA
Darke
Chris
C
Wordsworth
B Paul
BP
D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012680:Sensitivity and Specificity; D006113:United Kingdom / Q000453:epidemiology; D044465:White People / Q000235:genetics*
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens