TY - JOUR
T1 - Protective effect of human endogenous retrovirus K dUTPase variants on psoriasis susceptibility
AU - Lai, Olivia Y.
AU - Chen, Haoyan
AU - Michaud, Henri-Alexandre
AU - Hayashi, Genki
AU - Kuebler, Peter J.
AU - Hultman, Gustaf K.
AU - Ariza, Maria-Eugenia
AU - Williams, Marshall V.
AU - Batista, Mariana D.
AU - Nixon, Douglas F.
AU - Foerster, John
AU - Bowcock, Anne M.
AU - Liao, Wilson
N1 - Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012
Y1 - 2012
N2 - Previous genetic and functional studies have implicated the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the major histocompatibility complex region as a candidate psoriasis gene. Here, we describe a variant discovery and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy controls. Five common HERV-K dUTPase variants were found to be highly associated with psoriasis, with the strongest association occurring at the missense single-nucleotide polymorphism (SNP) rs3134774 (K158R, P=3.28 × 10 , odds ratio =2.36 (95% confidence interval: 1.91-2.92)). After adjusting the association of the HERV-K dUTPase variants for the potential confounding effects of HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and rs3134774 remained significantly associated. Haplotype analysis revealed that HERV-K haplotypes containing the non-risk alleles for rs3134774 and rs9264082 significantly reduced the risk of psoriasis. Functional testing showed higher antibody responses against recombinant HERV-K dUTPase in psoriasis patients compared with controls (P
AB - Previous genetic and functional studies have implicated the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the major histocompatibility complex region as a candidate psoriasis gene. Here, we describe a variant discovery and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy controls. Five common HERV-K dUTPase variants were found to be highly associated with psoriasis, with the strongest association occurring at the missense single-nucleotide polymorphism (SNP) rs3134774 (K158R, P=3.28 × 10 , odds ratio =2.36 (95% confidence interval: 1.91-2.92)). After adjusting the association of the HERV-K dUTPase variants for the potential confounding effects of HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and rs3134774 remained significantly associated. Haplotype analysis revealed that HERV-K haplotypes containing the non-risk alleles for rs3134774 and rs9264082 significantly reduced the risk of psoriasis. Functional testing showed higher antibody responses against recombinant HERV-K dUTPase in psoriasis patients compared with controls (P
UR - http://www.scopus.com/inward/record.url?scp=84862313453&partnerID=8YFLogxK
U2 - 10.1038/jid.2012.69
DO - 10.1038/jid.2012.69
M3 - Article
C2 - 22437317
SN - 0022-202X
VL - 132
SP - 1833
EP - 1840
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 7
ER -
