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Please use this identifier to cite or link to this item: http://hdl.handle.net/10373/227

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Title: Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases
Authors: Smith, Gillian
Wolf, C. Roland
Deeni, Yusuf Y.
Dawe, Robert S.
Evans, Alan T.
Comrie, Muriel M.
Ferguson, James
Ibbotson, Sally H.
Affiliation: University of Abertay Dundee. School of Social and Health Sciences
Keywords: Skin diseases
Issue Date: Apr-2003
Publisher: Elsevier Science B.V., Amsterdam.
Type: Journal Article
Refereed: peer-reviewed
Rights: Published version (c)Elsevier Science B.V., available from DOI: 10.1016/S0140-6736(03)13081-4
Citation: Smith, G., et al. 2003. Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases. The Lancet. 361(9366): pp.1336-1343. [Online] Available from: DOI: 10.1016/S0140-6736(03)13081-4
Abstract: Summary Background Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemo-therapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies. Methods We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis. Findings We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3·38 [95% CI 2·64–4·34] times higher; p<0·0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme. Interpretation These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.
URI: http://hdl.handle.net/10373/227
ISSN: 0140-6736
Appears in Collections:Social & Health Sciences Collection

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