Smoking, Genetics and RA
Recently, several genetic risk factors for the development of rheumatoid arthritis have been identified, yet none of them has as strong an association as does the “shared epitope” alleles at the HLA-DRB1 locus within the major histocompatibility complex. Because only about 30 percent of identical twins both develop rheumatoid arthritis (RA), it is clear that some environmental or other nongenetic factors must be at play in the susceptibility of RA. Cigarette smoking has now been established as one of those environmental factors that has a clear relationship with RA onset.
What Problem Was Studied?
Arthritis Foundationfunded researchers Lindsey A. Criswell, MD, MPH, Kenneth G. Saag, MD, MSc, and Ted R. Mikuls, MD, MSPH, along with a multicenter team of investigators, sought to take this information on risk factors a step further toward understanding the whole picture of RA risk. Glutathione S-transferases (GSTs) are believed to have an important role in detoxifying harmful components in cigarette smoke. So, they decided to look at the relationships among the shared epitope, a gene that regulates GSTs (GSTM1), smoking and the presence of RA. They theorized that those who do not express GSTM1 and smoke may have a particularly high risk of developing RA because they would have less detoxifying GSTs in their bodies.
What Was Done in the Study?
The Iowa Women’s Health Study, established in 1986, served as the source of study participants. A total of 115 white women with RA and 466 matched controls without RA were selected. DNA was collected and smoking data – including age started, age stopped and number of cigarettes smoked per day – were obtained.
What Were the Study Results?
The research team found that carrying the shared epitope, having an inactive GSTM1 gene and smoking were each associated with an increased likelihood of developing RA.
When the different factors were considered together, the results indicated that smoking was associated with a higher risk of RA development in postmenopausal white women without the shared epitope than in those with the shared epitope. Similarly, and contrary to the authors’ hypothesis, women with the active GSTM1 gene and who smoked had a higher risk than those women with the inactive GSTM1 gene who smoked. The authors concluded that, “In both situations the impact of smoking on RA risk operates primarily among subjects who lack these genetic risk factors.”
What Does This Mean for People At Risk For RA?
Whether you have a family history of RA or not, whether you carry the shared epitope or the inactive GSTM1 gene or not, don’t start smoking. Smoking can increase your risk of not only heart disease and cancer, but according to this study, rheumatoid arthritis as well. This study gives scientists insight into how environmental factors may interact with our genetic predisposition to increase our disease risk. The relationships between genetic susceptibility and environmental risk factors is a fertile area of research and will continue to receive attention in the future.
Learn more about how genes and your environment interact to affect your immune system and trigger arthritis.
Criswell LA, Saag KG, MilulsTR, et al. Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women. Ann Rheum Dis 2006;65:1163–7.