Asumalahti, Kati, Veal, Colin, Laitinen, Tarja, Suomela, Sari, Allen, Michael, Elomaa, Outi, Moser, Michael, De Cid, Rafael, Ripatti, Samuli, Vorechovsky, Igor, Marcusson, Jan A., Nakagawa, Hidemi, Lazaro, Conxi, Estivill, Xavier, Capon, Francesca, Novelli, Giuseppe, Saarialho-Kere, Ulpu, Barker, Jonathan, Trembath, Richard and Kere, Juha
Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus
Human Molecular Genetics, 11, (5), . (doi:10.1093/hmg/11.5.589).
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PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.
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