Rheumatoid arthritis is a chronic inflammatory autoimmune disease that affects approximately 0.5-1% of the general population and leads to chronic synovial inflammation, destruction of cartilage and bone, and disability. The heritability of rheumatoid arthritis has been estimated to be about 60%, while the contribution of HLA to heritability has been estimated to be 11-37%. Other genes, such as PTPN22, STAT4, CTLA4, TRAF1, PADI4, IRF5, FCRL3, TNFIP3, TNF-α, miRNAs, CD28, CD40, TYK2, etc., have been associated with susceptibility, severity, activity, and treatment response of rheumatoid arthritis. The aim of this review is to describe the role of gene variants located in immune system genes associated with susceptibility to rheumatoid arthritis.