In accordance, we observed an interaction between the major allele (C) of rs74058715, HLA-DRB1*04, and ever-smoking, as well as between the minor allele (T) of rs1748033 and HLA-DRB1*04 in increasing the risk of anti-CCP-positive RA. This evidence concerns the gene HLA-DRB1 and rheumatoid arthritis.