Identification of main genetic factors for certain rare manifestations of psoriasis

• Applicant: Professorin Dr. Ulrike Hüffmeier
• Subject Area: Human Genetics
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 237425291

Psoriasis is a common, chronic inflammatory skin disease. About one third of psoriasis patients develop a typical joint disease called psoriatic arthritis. Beside common manifestations of psoriasis, rare manifestations have been described that overlap in some clinical aspects. For a first rare form of psoriasis, called generalized pustular psoriasis (= GPP) and characterized by a severe skin manifestation and a multisystemic reaction, mutations in a gene coding for a receptor antagonist of interleukin-36 (IL36RN) of the interleukin-1 family have been identified recently. A further rare manifestation, resembling psoriasis in other aspects, is called SAPHO (syndrome of acne, pustulosis, hyperostosis and osteitis); its pathogenesis is unexplained. In order to identify further candidate genes for these two disease entities, exome sequencing of several GPP patients and SAPHO patients is planned. After validation, remaining variants will be analyzed in a control cohort. Analysis of databases and literature, explicit bioinformatics, expression analyses and functional studies will show whether those are disease-causing variants. To confirm the relevance of remaining genes and to correlate genotype and phenotype, the genes will also be tested in further GPP patients and SAPHO patients. As variants of the same genes could be involved in the pathogenesis of psoriasis complex disease manifestations, identified variants and further annotated non-synonymous variants are planned to be tested in our large psoriasis cohorts of psoriasis vulgaris patients and of psoriatic arthritis patients. Genes responsible for several psoriasis entities will be attractive starting-points for new immune-modulating therapies.

• DFG Programme: Research Grants