title: Association analysis identifies ZNF750 regulatory variants in psoriasis.
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.
authors.affiliation: Department of Dermatology, University of California, San Francisco, California, USA.
authors.forename: Ramon Y
authors.initials: RY
authors.lastname: Birnbaum
authors.forename: Genki
authors.initials: G
authors.lastname: Hayashi
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.forename: Annie
authors.initials: A
authors.lastname: Poon
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Lam
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008156:Luciferases; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D044465:White People / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D017931:DNA Primers; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C570799:ZNF750 protein, human; D008156:Luciferases