HLA-DRB1 and rheumatoid arthritis: A dramatically increased risk for ACPA-positive RA was seen in individuals who were both smokers and HLA-DRB1 SE positive (OR = 25.6; 95% CI, 10.4 to 63.4), and here we also observed a statistically significant gene-environment interaction between smoking and the HLA-DRB1 SE (AP = 0.7; 95% CI, 0.5 to 1.0; Figure 1).