Psoriasis study uncovers first interaction between genetic variants seen in humans
20 October 2010
Psoriasis is an autoimmune disease that affects 2-3 per cent of the European population. The disease occurs when the body's immune system incorrectly sends out signals that increase the rate by which skin cells divide. This can give rise to scaly patches on the skin that can be itchy and sometimes painful. Between one in five and one in ten people with psoriasis go on to develop psoriatic arthritis, an inflammatory joint disease.
There is currently no cure for this disease, which requires complex treatment. While the causes of the diseases are well understood, the genetic basis of the disease is not. The five studies out this week have identified specific regions of DNA that are involved with the disease.
In the first study (ref. 1), an international team of scientists from the Genetic Analysis of Psoriasis Consortium and the WTCCC2 carried out a genome-wide association (GWA) study of 2622 patients with psoriasis and 5667 healthy individuals from the UK in search of small DNA variations that could be important in the development of the disease. The study revealed eight regions of the human genome previously not known to be associated with psoriasis. Seven of these regions harbour genes with recognised immune functions. Six of the loci were confirmed in a European study of over 9000 people; the remaining two had a weaker association.
The study also found compelling evidence of interaction between two areas of DNA: the HLA-C and ERAP1 regions. In genetic terms, an interaction is when two independent regions of DNA, both important to a disease, are present and together substantially increase the chances of developing the disease. This is thought to be the first time that such an interaction has been identified in humans.
"We need to understand why psoriasis occurs and why individuals are more likely to develop the condition," explains Professor Richard Trembath from King's College London, co-leader of the study. "Through our research, and other studies now coming through, the research community have identified genes that play a role in people's susceptibility to the condition.
"This work provides evidence of possible targets for future treatment strategies and this information is an important basis for further studies."
In a second study (ref. 2), which also used data generated by the WTCCC, an international team of scientists led by Professor André Reis from the University of Erlangen-Nuremberg, Germany, found that the gene TRAF3IP2 increased susceptibility to both psoriasis and psoriatic arthritis. Their GWA study looked at 609 German individuals with psoriatic arthritis and 990 healthy individuals.
The WTCCC2 is a series of genome-wide association studies looking into 13 different conditions including ankylosing spondylitis, glaucoma, ischaemic stroke, multiple sclerosis and Parkinson's disease.
Image credit: Saynine on Flickr
References
1. Genetic Analysis of Psoriasis Consortium and the Wellcome Trust Case Control Consortium 2. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nature Genetics; e-pub 17 Oct 2010.
2. Hüffmeier U et al. Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nature Genetics; e-pub 17 Oct 2010.
