The gene encodes a protein called plakophilin 2, which is crucial for the formation and proper functioning of the skin structure, suggesting an aberrant skin barrier as a potential risk factor for atopic dermatitis.
Details appear today in the open-access journal PLoS Genetics.
Atopic dermatitis (or eczema) is an inflammatory, relapsing non-contagious skin disease affecting about 10-30 percent of the human population. It is not only humans that suffer from the disease: about 3-10 percent of dogs are also affected. The skin of a patient with atopic dermatitis becomes easily irritated by various allergens such as certain types of food, pollens or house mites. Such irritation causes very strong itching which leads to scratching, redness and flaky skin that becomes vulnerable to bacterial and yeast infections.
To-date, despite many scientific efforts, little has been known about the genetics of the disease. In their study, researchers from Uppsala University, SLU and Broad Institute, compared DNA samples from a large group of German shepherd dogs affected by atopic dermatitis with DNA coming from healthy dogs to reveal the specific DNA segment associated with the disease.
“With the help of pet owners, we have managed to collect a unique set of DNA samples from sick and healthy dogs which allowed us to gain insight into atopic dermatitis genetics,” said first author Katarina Tengvall, Uppsala University.
Purebred dogs such as German shepherds have been selected for specific physical features for several generations. Selection led to an inadvertent enrichment for disease-risk genes in certain breeds. Moreover, the resulting architecture of canine DNA makes it easier to pinpoint segments that carry these disease risk-genes. This helped the researchers to reveal the genetics of atopic dermatitis. They found a region associated with the atopic dermatitis containing the gene PKP-2, which encodes Plakophilin-2, a protein involved in the formation and maintaining of the proper skin structure.
“The finding that certain variants of the PKP-2 gene may increase the risk of developing the disease opens new possibilities in understanding the disease mechanism leading to atopic dermatitis,” continues Katarina Tengvall.
These findings will not only lead to better understanding of the disease, which may lead to better treatment strategies long term. It also opens up the possibilities of development of a genetic test for the disease.
“Our study suggests that plakophilin-2 and an intact skin barrier is important to avoid atopic dermatitis”, says senior author, Kerstin Lindblad-Toh, professor at Uppsala University and Director of SciLifeLab Uppsala. “Another gene involved in the skin barrier has recently been linked to human atopic dermatitis emphasizing the similarity between canine and human atopic dermatitis” continues Kerstin Lindblad-Toh.
Tengvall K, Kierczak M, Bergvall K, Olsson M, Frankowiack M, et al. (2013) Genome-Wide Analysis in German Shepherd Dogs Reveals Association of a Locus on CFA 27 with Atopic Dermatitis. PLoS Genet 9(5): e1003475. doi:10.1371/journal.pgen.1003475