Two Genes Linked to RA
While scientists don’t know what causes RA, they do know that in most, if not all, cases a genetic component is involved. In an exciting development, scientists have just announced two major new findings that link specific genes to the development of RA. Details of these findings, made possible in part by funding from the Arthritis Foundation, appeared in the New England Journal of Medicine.
These new findings are the culmination of work begun more than a decade ago by the North American Rheumatoid Arthritis Consortium (NARAC), a joint venture of the Arthritis Foundation and National Institute of Health to collect, analyze and make available clinical and genetic data on 1,000 sibling pairs with RA.
The first report identifies a genetic variant of STAT4 – a gene that plays important roles in the regulation and activation of the immune system – that puts people at significantly greater risk not only for RA but for lupus and perhaps other autoimmune diseases as well. Earlier, scientists had identified a region of a chromosome where risk genes for RA were likely located, says Peter Gregersen, MD, of the Feinstein Institute for Medical Research in Manhassett, N.Y. Dr. Gregersen is also principal investigator of NARAC. By knowing where to look, the scientists then tested 13 genes in the region and found single nucleotide polymorphisms (SNPs), small differences in DNA, in a large segment of STAT4.
Everyone has the STAT4 gene, but scientists have found that people who carry two copies of this particular variant of the gene have a 60-percent increased risk for RA and a 2.4-fold increased risk for lupus compared with people who carry no copies of the gene variant.
The second report describes the identification of a region on another chromosome containing two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5).
Scientists don't yet know which of the two genes that influence inflammation raise th risk of RA, or if possibly both are to blame, says Dr. Gregersen. Prior to these new findings, two other genes – PTPN22 and HLA-DRB1 – were known to confer risk for RA. But Dr. Gregersen believes as many as 10 to 20 genes will eventually be found to play a role in the disease.
Among people who have these risk genes, some type of infection or other environmental factor likely triggers the disease.
Researchers say it’s too soon to predict the clinical implications of the new findings. The hope is that by learning more about the genes, scientists may find clues to more effectively treating the disease. “I am almost certain that [genetic findings such as these] are going to allow us to characterize people better,” says Dr. Gregersen. “It’s this whole area of personalized medicine, selecting the right therapy for the right person.” A better knowledge of the genes involved may one day assist doctors in customizing treatment according to each person’s genetic profile.
How genes and your environment may interact to cause arthritis
Back to Focus on RA
