Genetic analysis of susceptibility to AS and RA suggests a polygenic inheritance pattern with the largest contribution from the major histocompatibility complex (MHC).[1,2] The MHC genetic contribution to these diseases is due to association of several alleles of the human leukocyte antigen (HLA)-DRB1 gene with RA and the HLA allele B27 with AS. The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.