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- Title
Protective Effect of Human Endogenous Retrovirus K dUTPase Variants on Psoriasis Susceptibility.
- Authors
Lai, Olivia Y; Chen, Haoyan; Michaud, Henri-Alexandre; Hayashi, Genki; Kuebler, Peter J; Hultman, Gustaf K; Ariza, Maria-Eugenia; Williams, Marshall V; Batista, Mariana D; Nixon, Douglas F; Foerster, John; Bowcock, Anne M; Liao, Wilson
- 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.
- Subjects
HUMAN endogenous retroviruses; PSORIASIS; DISEASE susceptibility; SKIN disease genetics; PHOSPHATASES; SINGLE nucleotide polymorphisms; IMMUNOGLOBULINS
- Publication
Journal of Investigative Dermatology, 2012, Vol 132, Issue 7, p1833
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2012.69