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 for the primary disease association but merely permissive for the susceptibility conferred by the HLA-DQ alleles with which they are in linkage disequilibrium. We have performed a critical review of the literature on the HLA association in RA with special emphasis on studies in which both an HLA-DR and -DQ association has been investigated. Our analyses provide 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.
Fugger
L
L
Department of Clinical Immunology, National University Hospital, Copenhagen, Denmark. fugger@inet.uni-c.dk
Svejgaard
A
A
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans
D006683:HLA-DQ Antigens; C069546:HLA-DQ7 antigen; C109756:HLA-DQ8 antigen; D015804:HLA-DR4 Antigen