Interestingly, it has been reported that while there is an interaction of ACPA positivity, HLA-DRB1 SE, and smoking as risk factors for RA, the association of smoking with RA disease in RF+ CCP2- individuals is largely independent of HLA-DRB1 SE, suggesting different modes of induction (59, 60). The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.