Psoriasis study uncovers first interaction between genetic variants seen in humans

Genetic variants associated with increased susceptibility to psoriasis, a chronic and recurrent skin disease, are reported in five papers published online in Nature Genetics this week. One paper, part of the Wellcome Trust Case Control Consortium 2 (WTCCC2), reports an interaction between two genetic regions - the first time that such an interaction has been seen in humans.

Psoriasis is an autoimmune disease psoriasis which affects 2-3% of the European population. The disease occurs when the body's immune system incorrectly sends out signals which increase the rate by which skin cells divide. This can give rise to scaly patches on the skin which 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. Whilst 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.


Oct 10 Gene interaction

In the first study1, an international team of scientists from the Genetic Analysis of Psoriasis Consortium and the WTCCC2 carried out a genome-wide association (GWA) study of 2,622 patients with psoriasis and 5,667 healthy individuals from the UK in search of small DNA variations which 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 recognized immune functions. Six of the loci were confirmed in a European study of over 9,000 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 - in this case, the genetic variant at HLA-C and ERAP1 - 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 study2, 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 thirteen different conditions including ankylosing spondylitis, glaucoma, ischaemic stroke, multiple sclerosis and Parkinson's disease.