TY - JOUR
T1 - Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus
AU - Psoriasis Consortium
AU - Veal, C
AU - Laitinen, T
AU - Suomela, S
AU - Allen, M
AU - Elomaa, O
AU - Moser, M
AU - de Cid, R
AU - Ripatti, S
AU - Vorechovsky, I
AU - Marcusson, J A
AU - Nakagawa, H
AU - Lazaro, C
AU - Estivill, X
AU - Capon, F
AU - Novelli, G
AU - Saarialho-Kere, U
AU - Barker, J
AU - Trembath, R
AU - Kere, J
PY - 2002/3/1
Y1 - 2002/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=18344372557&partnerID=8YFLogxK
U2 - 10.1093/hmg/11.5.589
DO - 10.1093/hmg/11.5.589
M3 - Article
SN - 1460-2083
VL - 11
SP - 589
EP - 597
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 5
ER -