The area includes C5 and TRAF1 genes and binds transcription factors.

Investigators found a consistent association between one specific region on chromosome 9 and rheumatoid arthritis (RA). The region includes two genes—complement component 5 (C5), previously implicated in a mouse study, and TNF receptor-associated factor 1 (TRAF1), a gene involved in the inflammatory response.


Prior research showed an association of RA in humans with the part of the genome that contains the human leukocyte antigens (HLAs). The scientists took 40 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 290 patients with RA and 254 unaffected participants of Dutch origin. They then repeated the study in three other groups of patients and controls of Dutch, Swedish, and U.S. origin.


The investigators say that they found a consistent association with RA of one region of 65 kbp that included one end of the C5 gene and the TRAF1 gene. They then reportedly refined the area of interest to a piece marked by one particular SNP that lay between the genes.


The team went on to show that the genetic region in which these genes are located may be involved in the binding of a protein that modifies the transcription of genes. Furthermore, they showed that one of the alternate versions of the marker in this region was associated with more aggressive disease.


The research was performed by Leiden University Medical Center, the Karolinska Institute, and Celera. It is published in the September 18 issue of in PLoS Medicine.

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