The combination of smoking and the HLA-DRB1*04:05 SE allele was also associated with an increased risk of ACPA-positive RA (OR = 12.9; 95% CI, 4.7 to 35.3; Table 5), and signs of interaction were seen, albeit statistically insignificant (AP = 0.4; 95% CI, -0.1 to 0.9). This evidence concerns the gene HLA-DRB1 and rheumatoid arthritis.