Although the exact cause of rheumatoid arthritis (RA) is not known, it has become increasing clear that this disease has both genetic and environmental origins. In December 2005, an international team of scientists released results of their study in the American Journal of Human Genetics examining several genes that may increase a person’s risk of developing RA. People with a specific group of genes called HLA-DRB1 (also known as the shared epitope) already were known to have an increased risk of developing RA. Now it has been determined that at least one other gene increases the likelihood of developing RA, and possible connections were found for two more.

Researchers verified a statistically significant association between having rheumatoid factor-positive RA and carrying a gene called PTPN22. The presence of PTPN22 also influenced age of onset of RA; those with the gene developed RA two years earlier than those without it. Two other genes, CTLA4 and PADI4, also had a positive association with the likelihood of developing RA, but the relationships were not as strong as with PTPN22, and the results will need to be confirmed in future studies.

Detecting the influence of genes on the disease in such a statistically significant way is a feat that has been difficult to achieve before now. The scientists had the power to succeed this time because they tested such a large number of people. In all, 17 genetic segments were tested in 2,370 people with RA and 1,757 people without RA from the North American Rheumatoid Arthritis Consortium, a research collaboration co-funded by the National Institutes of Health and the Arthritis Foundation, and the Swedish Epidemiological Investigation of Arthritis cohorts.