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Specific location of the TRAF1/C5 gene associated with multiple autoimmune diseases

June 16, 2008

The TRAF1/C5 locus on chromosome 9 has been revealed to play a role in multiple autoimmune diseases including type 1 diabetes and systemic lupus erythematosus (SLE), according to new data presented today at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France.

TRAF1 (Tumour Necrosis Factor-receptor associated factor 1) and C5 (complement component 5) are both immune related genes thought to be closely involved in the onset and/or perpetuation of the inflammatory process. They sit adjacent to one another on chromosome 9 at location q33-34. The TRAF1/C5 gene has previously been established as a genetic risk factor for rheumatoid arthritis. In this study, a further link was also found between the gene locus and the presence of autoantibodies (antibodies against antigens naturally occurring in the human body commonly found in patients with immune disorders). Since many autoimmune disorders tend to coexist within a given family as well as an individual, this indicates that there may be a common genetic pathway - something the researchers were keen to investigate.

In this study, genotyping of 735 type 1 diabetes patients and 746 SLE patients from Spain and The Netherlands identified a significant association of one part of the TRAF1/C5 gene with type 1 diabetes (odds ratio 1.14, p=0.027) and SLE (odds ratio 1.16, p=0.016). In order to test the reliability of this finding, researchers replicated the test in a homogeneous patient population originating from Crete, where an increase in the same part of the TRAF1/C5 gene was also observed when compared to respectively matched controls (odds ratio 1.64, p=0.002; odds ratio 1.43, p=0.002).

Lead researcher, Ms Fina Kurreeman of Leiden University Medical Center in The Netherlands, said, "The results of our study have shown that the TRAF/1C5 gene locus may have an important role in multiple autoimmune diseases. We hope that further study will give an insight into potential shared genetic pathways across autoimmune disorders and may even stimulate innovation into novel therapeutic targets in the future."

A further joint analysis of all type 1 diabetes (n=834)) and SLE patients (n=1018) patients yielded a common odds ratio of 1.19 (p=0.002) and 1.22 (p<0.001) respectively, indicating that this genetic risk factor has modest effect sizes in these diseases.

European League Against Rheumatism

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