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BMC Medical Genetics

, 12:167

Genetic epidemiology and genetic associations


BackgroundMutations 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.

MethodsWe 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.

ResultsWe 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.

ConclusionsTwo 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-167 contains supplementary material, which is available to authorized users.

Ramon Y Birnbaum, Genki Hayashi contributed equally to this work.

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Autor: Ramon Y Birnbaum - Genki Hayashi - Idan Cohen - Annie Poon - Haoyan Chen - Ernest T Lam - Pui-Yan Kwok - Ohad S Birk -


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