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Human Molecular Genetics, 2000, Vol. 9, No. 10 1533-1542
© 2000 Oxford University Press

A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with a disease-associated susceptibility allele

Kati Asumalahti, Tarja Laitinen, Raija Itkonen-Vatjus1, Marja-Liisa Lokki2, Sari Suomela3, Erna Snellman4, Ulpu Saarialho-Kere3 and Juha Kere5,+

Department of Medical Genetics, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland, 1Department of Dermatology, Oulu University Central Hospital, 90401 Oulu, Finland, 2Finnish Red Cross Blood Transfusion Service, Department of Tissue Typing, 00310 Helsinki, Finland, 3Department of Dermatology, Helsinki University Central Hospital, 00250 Helsinki, Finland, 4Department of Dermatology, Central Hospital of Päijät-Häme, 15850 Lahti, Finland and 5Finnish Genome Center, University of Helsinki, 00014 Helsinki, Finland

A susceptibility gene for psoriasis, a chronic skin disorder, resides in chromosome 6p near the HLA-C locus. Sequencing of the region has allowed the identification of a new gene, HCR. We found that HCR is highly polymorphic with at least 12 coding variants. An association study of the new HCR polymorphisms and the previously suggested susceptibility alleles HLA-Cw*0602 and corneodesmosin allele 5 (CD*5) with psoriasis revealed a specific HCR variant associated with psoriasis susceptibility. However, the HLA-Cw*0602 allele was rarer in controls and associated with a stronger relative risk. Association analysis did not support CD*5 as a psoriasis susceptibility allele in our sample of patients (n = 100) and population-matched controls (n = 93) from an isolated population. We found HCR to be overexpressed in keratinocytes of psoriatic lesions compared with paired samples of healthy skin. Our results suggest a potential role for HCR in the pathogenesis of psoriasis.

+ To whom correspondence should be addressed. Tel: +358 9 191 26538; Fax: +358 9 191 26789; Email: juha.kere@helsinki.fi


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