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

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

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)589 - 597
Number of pages9
JournalHuman Molecular Genetics
Volume11
Issue number5
DOIs
Publication statusPublished - 1 Mar 2002

Fingerprint

Dive into the research topics of 'Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus'. Together they form a unique fingerprint.

Cite this