The genetic contribution to the pathogenesis of rheumatoid arthritis.

The association of HLA-DR4 or other HLA-DRB1 alleles excoding the shared (or rheumatoid) epitope has now been established in nearly every population. Similarly, the fact that the presence and gene dosage of HLA-DRB1 alleles affect the course and outcome of rheumatoid arthritis has likewise been seen in most (although not all) studies. Family studies are making it increasingly clear that other genes are involved in the pathogenesis of rheumatoid arthritis, both within and outside of the major histocompatibility complex, and much work is ongoing to help identify them and their impact on the disease. This article reviews where we stand in the knowledge of HLA and other genes and their associations with predisposition to and outcome in rheumatoid arthritis.