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Open Access Research article

Association analysis identifies ZNF750 regulatory variants in psoriasis

Ramon Y Birnbaum123, Genki Hayashi4, Idan Cohen3, Annie Poon25, Haoyan Chen4, Ernest T Lam25, Pui-Yan Kwok25, Ohad S Birk3 and Wilson Liao4*

Author Affiliations

1 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA

2 Institute for Human Genetics, University of California, San Francisco, California, USA

3 The Morris Kahn Laboratory of Human Genetics, NIBN, Ben-Gurion University, Beer-Sheva, Israel

4 Department of Dermatology, University of California, San Francisco, California, USA

5 Cardiovascular Research Institute, University of California, San Francisco, California, USA

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BMC Medical Genetics 2011, 12:167  doi:10.1186/1471-2350-12-167

Published: 20 December 2011

Abstract

Background

Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene.

Methods

We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls.

Results

We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p < 0.05). We also identified an excess of rare promoter and 5'untranslated region (UTR) variants in psoriasis cases compared to controls (p = 0.041), whereas there was no significant difference in the number of rare coding and rare 3' UTR variants. Using a promoter functional assay in stimulated human primary keratinocytes, we showed that four ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families.

Conclusions

Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.