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Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy

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Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy. / Ibbotson, S. H.; Dawe, R. S.; Dinkova-Kostova, A. T.; Weidlich, S.; Farr, P. M.; Ferguson, J.; Wolf, C. R.; Smith, G.

In: British Journal of Dermatology, Vol. 166, No. 2, 02.2012, p. 380-388.

Research output: Contribution to journalArticle

Harvard

Ibbotson, SH, Dawe, RS, Dinkova-Kostova, AT, Weidlich, S, Farr, PM, Ferguson, J, Wolf, CR & Smith, G 2012, 'Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy' British Journal of Dermatology, vol 166, no. 2, pp. 380-388., 10.1111/j.1365-2133.2011.10661.x

APA

Ibbotson, S. H., Dawe, R. S., Dinkova-Kostova, A. T., Weidlich, S., Farr, P. M., Ferguson, J., ... Smith, G. (2012). Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy. British Journal of Dermatology, 166(2), 380-388. 10.1111/j.1365-2133.2011.10661.x

Vancouver

Ibbotson SH, Dawe RS, Dinkova-Kostova AT, Weidlich S, Farr PM, Ferguson J et al. Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy. British Journal of Dermatology. 2012 Feb;166(2):380-388. Available from: 10.1111/j.1365-2133.2011.10661.x

Author

Ibbotson, S. H.; Dawe, R. S.; Dinkova-Kostova, A. T.; Weidlich, S.; Farr, P. M.; Ferguson, J.; Wolf, C. R.; Smith, G. / Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy.

In: British Journal of Dermatology, Vol. 166, No. 2, 02.2012, p. 380-388.

Research output: Contribution to journalArticle

Bibtex - Download

@article{032c323f487c47ee933c6575a7a7ef12,
title = "Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy",
keywords = "Young Adult, Erythema, Photosensitivity Disorders, Polymorphism, Genetic, Dose-Response Relationship, Drug, Humans, Gene Expression, Glutathione Transferase, Aged, PUVA Therapy, Recurrence, Genotype, Glutathione S-Transferase pi, Photosensitizing Agents, Psoriasis, Methoxsalen, Oxidative Stress, Adult, Treatment Outcome, Middle Aged, Response Elements, Adolescent, Female, Male",
author = "Ibbotson, {S. H.} and Dawe, {R. S.} and Dinkova-Kostova, {A. T.} and S. Weidlich and Farr, {P. M.} and J. Ferguson and Wolf, {C. R.} and G. Smith",
note = "© 2011 The Authors. BJD © 2011 British Association of Dermatologists.",
year = "2012",
doi = "10.1111/j.1365-2133.2011.10661.x",
volume = "166",
number = "2",
pages = "380--388",
journal = "British Journal of Dermatology",
issn = "0007-0963",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy

A1 - Ibbotson,S. H.

A1 - Dawe,R. S.

A1 - Dinkova-Kostova,A. T.

A1 - Weidlich,S.

A1 - Farr,P. M.

A1 - Ferguson,J.

A1 - Wolf,C. R.

A1 - Smith,G.

AU - Ibbotson,S. H.

AU - Dawe,R. S.

AU - Dinkova-Kostova,A. T.

AU - Weidlich,S.

AU - Farr,P. M.

AU - Ferguson,J.

AU - Wolf,C. R.

AU - Smith,G.

PY - 2012/2

Y1 - 2012/2

N2 - Summary Background There is marked interpatient variation in responses to psoralen-ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability. The glutathione S-transferases (GSTs) influence cutaneous defence against UV radiation-induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk. Objectives To investigate the effect of GST genotype on PUVA sensitivity. Methods We investigated GST genotype in patients starting PUVA (n = 111) and the effects of 8-methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene expression in mammalian cells. Results Lower minimal phototoxic doses (MPD) (P = 0·022) and higher serum 8-MOP concentrations (P = 0·052) were seen in GSTM1-null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n = 50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15-1·64] and GSTT1-null (HR 2·39; 95% CI for HR 1·31-4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10-3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8-MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8-MOP metabolism. Conclusion The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings. © 2011 British Association of Dermatologists.

AB - Summary Background There is marked interpatient variation in responses to psoralen-ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability. The glutathione S-transferases (GSTs) influence cutaneous defence against UV radiation-induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk. Objectives To investigate the effect of GST genotype on PUVA sensitivity. Methods We investigated GST genotype in patients starting PUVA (n = 111) and the effects of 8-methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene expression in mammalian cells. Results Lower minimal phototoxic doses (MPD) (P = 0·022) and higher serum 8-MOP concentrations (P = 0·052) were seen in GSTM1-null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n = 50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15-1·64] and GSTT1-null (HR 2·39; 95% CI for HR 1·31-4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10-3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8-MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8-MOP metabolism. Conclusion The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings. © 2011 British Association of Dermatologists.

KW - Young Adult

KW - Erythema

KW - Photosensitivity Disorders

KW - Polymorphism, Genetic

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Gene Expression

KW - Glutathione Transferase

KW - Aged

KW - PUVA Therapy

KW - Recurrence

KW - Genotype

KW - Glutathione S-Transferase pi

KW - Photosensitizing Agents

KW - Psoriasis

KW - Methoxsalen

KW - Oxidative Stress

KW - Adult

KW - Treatment Outcome

KW - Middle Aged

KW - Response Elements

KW - Adolescent

KW - Female

KW - Male

UR - http://www.scopus.com/inward/record.url?scp=84856226706&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2133.2011.10661.x

DO - 10.1111/j.1365-2133.2011.10661.x

M1 - Article

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 2

VL - 166

SP - 380

EP - 388

ER -

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