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    Hum Mol Genet. 2002 Mar 1;11(5):589-97.

    Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus.

    Asumalahti K, Veal C, Laitinen T, Suomela S, Allen M, Elomaa O, Moser M, de Cid R, Ripatti S, Vorechovsky I, Marcusson JA, Nakagawa H, Lazaro C, Estivill X, Capon F, Novelli G, Saarialho-Kere U, Barker J, Trembath R, Kere J; Psoriasis Consortium.

    Source

    Department of Medical Genetics and Finnish Genome Center, University of Helsinki, 00014 Helsinki, Finland.

    Abstract

    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.

    PMID:
    11875053
    [PubMed - indexed for MEDLINE]
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