Protective Effect of Human Endogenous Retrovirus K dUTPase Variants on Psoriasis Susceptibility

被引：20

作者：

Lai, Olivia Y. ^{[1
]}

Chen, Haoyan ^{[1
]}

Michaud, Henri-Alexandre ^{[2
]}

Hayashi, Genki ^{[1
]}

Kuebler, Peter J. ^{[2
]}

Hultman, Gustaf K. ^{[2
]}

Ariza, Maria-Eugenia ^{[3
,4
]}

Williams, Marshall V. ^{[3
,4
,5
]}

Batista, Mariana D. ^{[2
,6
]}

Nixon, Douglas F. ^{[2
]}

Foerster, John ^{[7
]}

Bowcock, Anne M. ^{[8
]}

Liao, Wilson ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA

[3] Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

[4] Ohio State Univ, Med Ctr, Inst Behav Med Res, Columbus, OH 43210 USA

[5] Ohio State Univ, Med Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA

[6] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo, Brazil

[7] Univ Dundee, Med Educ Inst, Coll Med Dent & Nursing, Dundee, Scotland

[8] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2012年 / 132卷 / 07期

基金：

美国国家卫生研究院;

关键词：

HLA-C; LOCUS PSORS1; HAPLOTYPE; ASSOCIATION; DISEASE; GENE; POPULATION; SEQUENCE; PROTEIN; SKIN;

D O I：

10.1038/jid.2012.69

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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 x 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. Journal of Investigative Dermatology (2012) 132, 1833-1840; doi:10.1038/jid.2012.69; published online 22 March 2012

引用

页码：1833 / 1840

页数：8

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