Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis.

The cause and pathogenesis of rheumatoid arthritis (RA) are influenced by environmental and genetic risk factors. Shared epitope-coding human leukocyte antigen (HLA)-DRB1 alleles increase RA risk and severity; however, the underlying mechanisms of action remain unclear. In contrast, several other DRB1 alleles protect against RA. Additionally, genome-wide association studies suggest that RA associates with other, HLA and non-HLA, genes; but the relative contributions of such risk loci to RA are incompletely understood. Future research challenges include integrating the epidemiologic and genomic data into validated arthritogenic pathways and determining the mechanisms of interaction between RA risk genes and environmental influences.