HLA genes as a model for genomic medicine for rheumatoid arthritis

Abstract

Both genetic predisposition and environmental factors are involved in the development of rheumatoid arthritis（RA）. Based on epidemiological studies such as twin studies, the influence of genetic factors on the development of RA has been estimated to be about 50%. Among the genes associated with RA, the human leukocyte antigen（HLA）gene demonstrates the largest contribution. The HLA-DRB1 allele, which encodes an HLA-DR beta chain containing a five-amino acid sequence motif called a “shared epitope”（SE）, has traditionally been associated with RA. Recent genetic analysis has identified five amino acids in the HLA molecule that are particularly important in the association with RA, and the understanding of the association is steadily progressing. Interpreting the contribution of HLA is an important step in translating genomic information to clinical practice in RA. This review summarizes the relationship between HLA molecules and pathological or clinical parameters in RA.