title: Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus.
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.
authors.affiliation: Department of Medical Genetics and Finnish Genome Center, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Asumalahti
authors.forename: Colin
authors.initials: C
authors.lastname: Veal
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
authors.forename: Sari
authors.initials: S
authors.lastname: Suomela
authors.forename: Michael
authors.initials: M
authors.lastname: Allen
authors.forename: Outi
authors.initials: O
authors.lastname: Elomaa
authors.forename: Michael
authors.initials: M
authors.lastname: Moser
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Igor
authors.initials: I
authors.lastname: Vorechovsky
authors.forename: Jan A
authors.initials: JA
authors.lastname: Marcusson
authors.forename: Hidemi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Conxi
authors.initials: C
authors.lastname: Lazaro
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Francesca
authors.initials: F
authors.lastname: Capon
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Ulpu
authors.initials: U
authors.lastname: Saarialho-Kere
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barker
authors.forename: Richard
authors.initials: R
authors.lastname: Trembath
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: C412616:CCHCR1 protein, human; D006023:Glycoproteins; D015236:HLA-C Antigens; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins