VIENNA, Austria-An individual's risk for developing rheumatoid arthritis (RA) can be accounted for by a combination of genetic and environmental risk factors. If, in fact, components of the environmental effect on RA pathogenesis are reversible, efforts to avoid these stimuli may reduce risk. Epidemiologist Alan Silman, MD, professor of rheumatic disease epidemiology at the University of Manchester in the UK, speaking here Thursday at the Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR),1 points to the success of risk-reduction strategies in areas such as cardiovascular disease, and asks the provocative question, "Is RA preventable?" Indeed, he suggests that a large portion of RA risk may be.
The first step toward answering this question, he asserts, is a determination of how much of one's risk for developing RA is the result of unmodifiable genetic factors. Separate studies from the UK and Finland examining the incidence of RA among monozygotic (MZ or identical) twins and dizygotic (DZ or fraternal) twins arrived at the same conclusion: genetics are responsible for about half the incidence of RA. "So, the question is," Dr. Silman asks, "in rheumatoid arthritis, can we identify what an epidemiologist would call 'risk factors', and are those risk factors reversible?"
He enumerates a variety of modifiable environmental effects that epidemiologic studies have found to be linked with the occurrence of RA, suggesting that, in fact, some risk may be reversed.
Oral contraceptive use has been shown to reduce the risk of RA by 50%, but Dr. Silman points out that it is unclear whether this is an actual absolute reduction, or whether this is simply the effect of delaying pregnancy. He also cites data indicating that a variety of lifestyle factors contribute to RA risk, with cigarette smoking the most prominent. One study of Norwegian men demonstrated that smoking causes a 10-fold increase in risk for RA, and other studies have shown that even exposure to second-hand smoke can cause a 1.7 fold elevated risk. Furthermore, in MZ twins, smoking confers a 12-fold increase in risk if the identical sibling has RA.
Dr. Silman also cites data that diet can influence RA risk. For instance, evidence suggests that the Mediterranean diet and antioxidants have a protective effect. However, previous infection, particularly with Epstein-Barr virus (EBV), is thought to increase risk.
Dr. Silman was also cochair of session entitled "Tools for Prediction of Diagnosis and Prognosis of RA."2 One of the panelists and cochairs, Tom WJ Huizinga, MD, PhD, professor of rheumatology at Leiden University Medical Center, in The Netherlands, discussed the known genetic risk factors for RA, including the PTPN22 SNP, which lowers the threshold of T-cell activation, and the HLA-DRB1 alleles implicated in the shared epitope hypothesis. These genotypes are thought to predispose carriers to more severe disease progression by increasing the likelihood of anticyclic citrullinated peptide (anti-CCP)-positive RA.
When asked how these genetic factors may interact with the environmental factors he discussed in the prevention of RA, Dr. Silman tells CIAOMed that "RA is a disease that is multifactorial," referring to the multihit hypothesis put forward by Dr. Huizinga. "I think genetic factors may, for example, help identify people at risk who also have an environmental exposure like cigarette smoking," he notes. "Even if you have all the bad genes, there is still an environmental component on top."
References:
- Silman A. Rheumatoid arthritis, possibilities for prevention, primary and secondary. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Plenary Session: Advances in major rheumatic diseases.
- Huizinga TWJ. Genetics as a tool for prediction in RA, diagnosis and prognosis. Presented at: Annual European Congress of Rheumatology; June 8-11, 2005; Vienna, Austria. Plenary Session: Tools for the prediction of diagnosis and prognosis of RA.