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.

RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

“…The human HCR gene maps to chromosome 6p21, in a region that is crucial for psoriasis vulgaris, located 111 kb towards the telomere of the HLA-C gene (Suomela et al, 2003). HCR is expressed differently in lesional psoriatic skin compared with normal skin (Asumalahti et al, 2002). HCR has also been identified as protein partner for StAR and hence has been named SBP (Sugawara et al, 2003).…”

“…The HCR gene was identified within the 111 kb telomeric region of the HLA-C gene, a crucial region for psoriasis vulgaris (Oka et al, 1999;Suomela et al, 2003). The direct involvement of HCR in psoriasis is currently being discussed (Asumalahti et al, 2000;O'Brien et al, 2001;Asumalahti et al, 2002;Elomaa et al, 2004). Using HCR-transgenic mice, a recent report suggested that HCR is a potential candidate gene for psoriasis susceptibility (Elomaa et al, 2004).…”

Psoriasis: genetic associations and immune system changes

“…Two genes lying within this interval have been intensively studied with respect to their role in psoriasis susceptibility. One is HCR (helix coiled coil rod homolog); 42 the other is corneodesmosin (CDSN/S). CDSN is expressed in terminally differentiated keratinocytes and in the inner root sheath of hair follicles.…”

Possible relations between the polymorphisms of the cytokines IL-19, IL-20 and IL-24 and plaque-type psoriasis

“…4,5 The susceptibility region in chromosome 6 (PSORS1-psoriasis susceptibility 1) has refined to an approximately B300 kb region around HLA-C gene and contains several candidate genes including HLA-C, octamer transcription factor-3 (OTF3), transcription factor-19 (TCF19), corneodesmosin (CDSN) and a-helix coiled-coil rod homolog (HCR) genes. [6][7][8][9] In addition, several non-MHC psoriasis susceptibility loci (1q21, 16q and 17q) associate with different AIDs such as systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and diabetes. 10 This provides support for the hypothesis that susceptibility to different AIDs may be driven by the same susceptibility genes and immunopathways.…”