It increases the body’s oxidative stress, interferes in apoptosis, provokes proinflammatory processes, and causes citrullination, and epigenetic changes, such as DNA methylation.98 It is evident that past and current cigarette smoking (CS) are related to the development of RA, in particular seropositive RA, where intensity and duration are directly related to the risk, with a prolonged increased risk even after cessation.99,100 A gene-environment interaction exists between smoking and the HLA-DRB1 SE genotype. Here, HLA-DRB1 is linked to rheumatoid arthritis.