We used MEDLINE for our literature search of the following terms: rheumatoid arthritis/RA, cigarette smoking, anti-citrullinated cyclic peptide/protein antibody/ACPA, rheumatoid factor/RF, HLA-DRB1, shared epitope allele, environmental risks, genetic risks, and single nucleotide polymorphisms/SNPs. The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.