Genetic etiology of psoriasis

Coordinator:    Dr. Eva Ellinghaus
Institution: Institut für KlinischeMolekularbiologie der Christian-Albrechts-Universität zu Kiel
The subproject GP6 aims at the identification of genetic susceptibility factors for psoriasis, an immune-mediated skin disease that can also affect nails and joints. About 2-3% of the Caucasian population suffer from psoriasis. The most common form, psoriasis vulgaris, affects about 90% of psoriasis patients and is characterized by red, raised, scaly plaques that commonly occur on the elbows, knees, scalp and lower back. Since psoriasis has a strong genetic background, it is our goal to characterize the genetic causes of disease pathogenesis, as a prerequisite for a customized therapy for this distressing disease.

Through genome-wide association studies, enabled by chip technology-based high-throughput screening of the genome of thousands of patients and healthy control subjects, 36 psoriasis risk genes/regions could be identified by now for the European population.

Within the framework of the subproject GP6, the identification of the disease gene TRAF3IP2 for both psoriasis and psoriatic arthritis is noteworthy, as not only a new risk gene but also a potential causative variant within the gene could be identified. This genetic variant changes an amino acid in a highly conserved putative peptide binding site of the encoded protein so that the interaction with other proteins is possibly altered. With the identification of this gene, the role of the pathogenesis-relevant IL-17 pathway was further corroborated. In December 2012, we published another large international study, including a total of 10,588 psoriasis patients and 22,806 healthy controls. With this study we identified 15 new risk loci, and in addition independent risk variants within five already known susceptibility regions were found. The newly identified chromosomal segments contain candidate genes that play a role in other autoimmune diseases, for example in the regulation of T cell functions, or the innate immune response. Due to genetic susceptibility factors shared among immune-mediated diseases, the focus is now on cross-phenotype analyzes across several diseases.

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