The HCR gene on 6p21 is unlikely to be a psoriasis susceptibility gene

The PSORS1 locus in the human major histocompatibility complex on 6p21 has been consistently associated with psoriasis in populations of diverse ethni city. 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 its elf. The alpha -helix coiled-coil rod homolog gene (NCR, previously Pg8) is located 110 kb from the HLA-C gene, positioned between the CDSN and SC1 ge nes, within a region thought to harbor a psoriasis gene (PSORS1). We invest igated the HCR gene for disease association by direct sequencing of nine po lymerase chain reaction products amplified from a series of Swedish psorias is 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 a nd HLA-Cw*0602 indicates that NCR cannot truly be considered a Likely candi date gene. We investigated Cw*0602 association while stratifying for HCR si ngle nucleotide polymorphisms. We also investigated NCR single nucleotide p olymorphism association with the disease while stratifying for the presence of Cw*0602, We found that whichever single nucleotide polymorphism that wa s stratified for, there was still a strongly significant Cw*0602 associatio n with psoriasis; however, when we stratified for Cw*0602 presence, only on e silent polymorphism showed significant association. In a recent similar s tudy this polymorphism was actually found to be decreased in psoriasis indi viduals. Thus we conclude that HCR polymorphisms display association with p soriasis due to Linkage disequilibrium with Cw*0602 and is, therefore, unli kely to be directly involved in the development of psoriasis.