Protective effect of human endogenous retrovirus K dUTPase variants on psoriasis susceptibility

Olivia Y. Lai, Haoyan Chen, Henri Alexandre Michaud, Genki Hayashi, Peter J. Kuebler, Gustaf K. Hultman, Maria Eugenia Ariza, Marshall V. Williams, Mariana D. Batista, Douglas F. Nixon, John Foerster, Anne M. Bowcock, Wilson Liao

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19 Scopus citations

Abstract

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 × 10-15, 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<0.05), as well as higher T-cell responses against a single HERV-K dUTPase peptide (P<0.05). Our data support an independent role for the HERV-K dUTPase on psoriasis susceptibility, and suggest the need for additional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis.

Original languageEnglish
Pages (from-to)1833-1840
Number of pages8
JournalJournal of Investigative Dermatology
Volume132
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

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