In a paper published in September of 2007 edition of the online journal PLoS Medicine, an international team of scientists provided strong evidence that a particular section of the human genome is associated with rheumatoid arthritis. The team consisted of Dr. Rene Toes and colleagues from Leiden University Medical Center, the Karolinska Institute, and Celera.
In past experiments, evidence has shown an arthritic association in humans with the part of the genome that contains the human leukocyte antigens (HLAs), antigens that are heavily involved immune responses. In addition, previous work in mice that have a disease similar to human rheumatoid arthritis has identified a number of possible candidate genes. One of these genes, the complement component 5 (C5) is involved in the complement system, a primitive system within the body that is involved in the defense against foreign molecules. In humans, the gene for C5 is located on Chromosome 9 close to another gene involved in the inflammatory response, the TNF receptor-associated factor 1 (TRAF1).
For this study, the researchers began by studying a group of Dutch arthritis patients and matched them with controls. From these patients, the team took 40 genetic markers, single-nucleotide polymorphisms (SNPs), from across the region that included the C5 and TRAF1 genes. They compared which of the alternate forms of the SNPs were present in the 290 patients with rheumatoid arthritis and the 254 unaffected participants.
The team then repeated the study in three other groups of patients and controls of Dutch, Swedish, and US origin. They found a consistent association with rheumatoid arthritis of one region of 65 kilobases (i.e. 65,000 base pairs of DNA) that included one end of the C5 gene as well as the TRAF1 gene; they further refined the area of interest to a piece of code marked by one particular SNP that lay between the genes.
In the end, the team is confident that they have found a consistent association with one specific region of the genome, which again is a region on chromosome 9 that includes the two genes, complement component 5 (C5) of the complement system and 1(TRAF1). Furthermore, the team was able to show that one of the alternate versions of the SNP markers in this region was associated with more aggressive disease. Further work will need to be done to confirm the association in other populations and then to identify the precise genetic change involved.
A Candidate Gene Approach Identifies the TRAF1/C5 Region as a Risk Factor for Rheumatoid Arthritis”, site accessed on 9/21/07.