Recent genetic studies have revealed several new sites of genes that are risk factors for developing rheumatoid arthritis (RA). The strongest association with anti-citrullinated protein antibody (ACPA)-positive RA (ACPAs are autoantibodies detected in RA that are used as a major diagnostic tool) has been found for the HLA-DRB1 gene, and this site seems to play a central role in susceptibility to the disease in Caucasian populations. Prior studies have shown a high increase in the risk of ACPA-positive RA linked to smoking in those who have certain variations of the HLA-DRB1 gene. There are several types of such alleles correlation to a particular amino acid sequence known as shared epitope (SE). ACPAs occur in about 60 percent of RA patients and are closely associated with the presence of SE alleles. In fact, SE alleles are the strongest genetic risk factor for ACPA-positive RA.Of several environmental factors that predispose people toward developing RA, smoking has been found to be the main risk factor and a strong gene-environment interaction between smoking and SE alleles for ACPA-positive patients has been shown in prior studies in Europe. Results in North America have not been as conclusive, however. A new large population-based study examined the gene-environment interaction between smoking and SE alleles in RA and observed that all SE alleles strongly interact with smoking in conferring an increased risk of ACPA-positive RA. The study was reported in the recent issue of Arthritis & Rheumatism.
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