Genetic influences in psoriasis are uncovered

By April Clarkson, May 5th, 2013 | Health | 0 Comments

The first comprehensive study of the genetics of psoriasis has shown seven sites on the human genome where there are variations linked to the disease. One of these links psoriasis with a complication called psoriatic arthritis and also four other autoimmune conditions.

Psoriasis is a chronic autoimmune disease in which the immune system attacks skin cells, resulting in red, scaly patches on the skin that are itchy and painful. Around 2-3 percent of the population is affected by psoriasis and 25 percent develop psoriatic arthritis which is a painful inflammation of the joints.

It is known that genetic factors are important in psoriasis because relatives of those with the disorder are at higher risk of developing it themselves than the rest of the population. Genetic variation in an area of the human genome linked to the multiple histocompatibility complex (MHC) has been noted previously in psoriasis. The MHC is important for the immune system distinguishing ‘self’ from ‘non self’ which clearly goes awry in psoriasis and other autoimmune diseases. But only around ten percent of those with MHC genetic variations actually develop psoriasis, which means other genetic effects and environmental factors are important too.

Researchers at the University of Washington, St Louis, Missouri, and colleagues elsewhere, have explored the genetic factor in psoriasis by doing a whole genome-scan. This approach, which has recently been used in other diseases like breast cancer, looks for variations called single nucleotide polymorphisms (SNPs) which may signal a gene important in a disease.

The study was carried out in two phases. In the initial, ‘discovery’ phase, a group of 132 patients with psoriasis and 91 with psoriatic arthritis gave DNA samples and had their whole genome scanned for relevant SNPs. A group of 519 healthy controls were used for comparison, to see which SNPs occurred only in the psoriasis group. Later, the results were confirmed with a bigger group of 577 individuals with psoriasis and 576 with psoriatic arthritis, who were compared to more than 1,200 healthy control subjects.

The genome-wide scan revealed seven SNPs associated with psoriasis. Four of these had previously been identified in smaller studies. The MHC association was confirmed in this study and a specific gene called HCP5 seems to play an important role. HCP5 has been shown to delay the onset of AIDS in people infected with HIV. Psoriasis can sometimes be triggered by HIV infection, so it may be that mounting a defense to the virus, through HCP5, also triggers the inflammation that leads to autoimmune disease.

SNPs on chromosome 4 were also identified in this study and these DNA variations have also been linked to other autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, Grave’s disease and celiac disease. This genome region contains genes for inflammatory molecules called interleukin2 and interleukin21 and suggests that drugs which block either or both of these might be useful new therapies for psoriasis.

New genetic variations were also discovered on chromosome 13, in a region involved in modifying proteins, and on chromosome 15, the location of a protein that modifies tumor necrosis factor (TNF), a molecule that plays an important role in psoriasis. Therapies that block TNF are used in psoriasis and other autoimmune diseases.

The genome-wide scan is a new tool in understanding the molecular nature of a disease. This study has shown some new pathways that might be involved in psoriasis and other autoimmune diseases. It opens up the possibility of a more personalized approach to therapy, where the individual’s genotype guides the choice of treatment. It could also help develop new treatments, like the TNF inhibitors, which act on molecular targets uncovered by genomic studies. For the patient, it means that the genetic influences involved in their disease is better understood which should improve both diagnosis and treatment.