title: The HCR gene on 6p21 is unlikely to be a psoriasis susceptibility gene.
abstract: The PSORS1 locus in the human major histocompatibility complex on 6p21 has been consistently associated with psoriasis in populations of diverse ethnicity. The HLA-C allele Cw*0602, located therein, has been found in up to 67% of psoriasis patients but is no longer considered a candidate gene in itself. The alpha-helix coiled-coil rod homolog gene (HCR, previously Pg8) is located 110 kb from the HLA-C gene, positioned between the CDSN and SC1 genes, within a region thought to harbor a psoriasis gene (PSORS1). We investigated the HCR gene for disease association by direct sequencing of nine polymerase chain reaction products amplified from a series of Swedish psoriasis patients and controls. We found that HCR is a very polymorphic gene with 25 polymorphisms in the open reading frame alone, of which 10 demonstrated disease association; however, the relationship between HCR polymorphisms and HLA-Cw*0602 indicates that HCR cannot truly be considered a likely candidate gene. We investigated Cw*0602 association while stratifying for HCR single nucleotide polymorphisms. We also investigated HCR single nucleotide polymorphism association with the disease while stratifying for the presence of Cw*0602. We found that whichever single nucleotide polymorphism that was stratified for, there was still a strongly significant Cw*0602 association with psoriasis; however, when we stratified for Cw*0602 presence, only one silent polymorphism showed significant association. In a recent similar study this polymorphism was actually found to be decreased in psoriasis individuals. Thus we conclude that HCR polymorphisms display association with psoriasis due to linkage disequilibrium with Cw*0602 and is, therefore, unlikely to be directly involved in the development of psoriasis.
authors.affiliation: Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: K P
authors.initials: KP
authors.lastname: O'Brien
authors.forename: S J
authors.initials: SJ
authors.lastname: Holm
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.forename: L
authors.initials: L
authors.lastname: Carlén
authors.forename: T
authors.initials: T
authors.lastname: Rosenmüller
authors.forename: C
authors.initials: C
authors.lastname: Enerbäck
authors.forename: A
authors.initials: A
authors.lastname: Inerot
authors.forename: M
authors.initials: M
authors.lastname: Ståhle-Bäckdahl
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D017124:Conserved Sequence; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D011565:Psoriasis / Q000209:etiology*; D012016:Reference Values
chemical_list: C412616:CCHCR1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins