Psoriasis is a chronic inflammatory immune-mediated disease that causes patches of skin to become flaky or sore. The current cause of the condition is unknown and it is estimated that 125 million people worldwide have psoriasis. Now, a new study by researchers at Wellcome Sanger Institute and collaborators reveals psoriasis is not caused or spread by spontaneous genetic mutations in the skin.
The researchers sequenced skin samples from 111 people with psoriasis. They didn’t find any mutated genes in the psoriatic patches that weren’t also mutated in the individual’s unaffected skin tissue.
The study is published in Nature Genetics in an article titled, “Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin.”
The findings suggest that unlike other inflammatory diseases, such as inflammatory bowel disease or chronic liver disease, somatic mutations were not responsible for the start or spread of psoriasis, which enables researchers to continue to explore other avenues.
The researchers took skin samples from the forearms of 111 people with psoriasis, taking samples from psoriasis patches and healthy skin. They used laser capture microdissection to isolate 1,182 samples, which were then analyzed by whole genome or exome sequencing.
They observed minimal differences in the types of mutations seen in healthy skin versus psoriasis patches and only a slight increase in the number of mutations. In addition to this, no functional differences were seen between psoriasis and non-psoriasis tissue, suggesting that the condition is not linked to a specific somatic mutation in the skin.
The team identified four new driver mutations that gave skin cells an advantage over their neighbors, all found in both psoriasis patches and other skin tissue.
“Studying somatic mutations in noncancerous conditions has only become possible recently thanks to technological advancements,” explained Sigurgeir Olafsson, PhD, first author previously from the Wellcome Sanger Institute, now at deCODE genetics. “Genetic analysis of noncancerous diseases can help identify new driver mutations, such as those we describe. This adds to our growing collective knowledge about the impact of mutations on cancer and other diseases, as well as showing that certain treatments can influence the mutational landscape of a tissue.”
