* update to post on 10-19-09. The American College of Rheumatology at their annual conference announced a recent focus on genetic research. See the following links: http://www.nxtbook.com/nxtbooks/tristar/acr09-day2/#/2, http://www.nxtbook.com/nxtbooks/tristar/acr09-day2/#/6
As mentioned in an earlier post, three factors, environmental, genetic, and a “leaky gut”, are suspected to play some role in rheumatoid arthritis. When in the process of being diagnosed, patients complete massive amounts of paperwork. Embedded within these forms are questions about family medical history. These questions are attempting to establish genetic propensity for autoimmune diseases. Doctors will ask new RA patients if anyone else in the family has a history of autoimmune diseases since there appears to be a connection. There is even a database designed to track these connections.[i] My mother had Hashimoto’s disease (hypothyroidism), my grandmother had psoriasis, and my great uncle was suspected of having ankylosing spondylitis. Whether or not there is any familial link is not certain but the fact that these disorders were present in my family increases the risk. For RA, the risk of closely related family members having the disease is about 4%.[ii]
Since the recent mapping of the human genome in 2003, scientists are starting to unravel genetic connections to a variety of diseases.[iii] There are 23 chromosomes, about 25,000 human genes, and over 3 billion chemical base pairs in the human genome. These base pairs contain the code for all of our characteristics. For the most part, all of us are strikingly similar genetically. Anytime there is a slight change in a genetic base pair sequence, it’s called a singular nucleotide polymorphism or SNP. This YouTube video provides a short and simple overview for the scientifically challenged. SNPs are what make all of us different. Hair color, height, and other characteristics (both external and internal) are determined by these slight genetic differences or SNPs.
A variety of SNPs have been linked with RA. Scientists in the UK and at MIT found a SNP called PTPN22 connected to a variety of autoimmune diseases including RA.[iv] [v] Other SNPs connected with RA include rs6920220 and rs5029937. [vi] [vii] [viii] Another group reported that a SNP on chromosome 17 is linked to proteins in the thymus gland which are connected to psoriasis, rheumatoid arthritis and systemic lupus erythematosus.[ix]
So what does this mean for the future of RA treatment? At this point it doesn’t mean much. But the fact that some genetic markers for RA are being identified brings hope that future treatments can be targeted at these SNPs. In an earlier post I mentioned that scientists at the University of Rochester identified that the NF-kappaB signaling pathway is involved with tumor necrosis factor (TNF). TNF is the target of many of the biological treatments like Enbrel, Humira, Remicade, Cimzia and Simponi. An article published in May 2009 suggests that genetic SNPs related to this pathway are of interest in RA and that scientists should “translate these discoveries to improve care of patients with RA.”[x] Initial experiments in transferring genes into the joints of RA patients show promise. [xi] [xii] [xiii] But time will tell and I wonder if those of us living with RA now will benefit from this work. In the meantime, we can marvel in our genetic differences.