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

doi:10.1038/jid.2012.69

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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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

Original language	English
Pages (from-to)	1833-1840
Number of pages	8
Journal	Journal of Investigative Dermatology
Volume	132
Issue number	7
DOIs	https://doi.org/10.1038/jid.2012.69
Publication status	Published - 2012

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Lai, O. Y., Chen, H., Michaud, H-A., Hayashi, G., Kuebler, P. J., Hultman, G. K., Ariza, M-E., Williams, M. V., Batista, M. D., Nixon, D. F., Foerster, J., Bowcock, A. M., & Liao, W. (2012). Protective effect of human endogenous retrovirus K dUTPase variants on psoriasis susceptibility. Journal of Investigative Dermatology, 132(7), 1833-1840. https://doi.org/10.1038/jid.2012.69

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title = "Protective effect of human endogenous retrovirus K dUTPase variants on psoriasis susceptibility",

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",

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

year = "2012",

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AU - Lai, Olivia Y.

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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

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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

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

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