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

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

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Authors

  • 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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Info

Original languageEnglish
Pages1833-1840
Number of pages8
JournalJournal of Investigative Dermatology
Journal publication date2012
Volume132
Issue7
DOIs
StatePublished

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 , 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

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