The HLA-DQ7 and -DQ8 associations in DR4-positive rheumatoid arthritis patients - A combined analysis of data available in the literature

Several different lines of evidence have demonstrated that inherited susceptibility to rheumatoid arthritis (RA) is associated with the DRB1 genes encoding the HLA-DR4 and HLA-DR1 molecules. A contrasting hypothesis has recently been proposed, suggesting that, in general, the DRB1 locus is associated with protection to RA and that the RA-associated DRB1 alleles are not responsible fur the primary disease association but merely permissive for the susceptibility conferred bq the HLA-DQ alleles with which they anl in linkage disequilibrium. We have performed a critical review of the literature on thr HLA association in RA with special emphasis on studies in which both an MLB-DR and -DQ association has been investigated, Our analyses protide strong evidence against the hypothesis that HLA-DQ molecules play a major role in the general susceptibility to RA. Thus, the strongest association in rheumatoid arthritis is with DRB1 genes rather than DQB1 genes.