Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy

Gillian Smith; Simone Weidlich; Robert S. Dawe; Sally H. Ibbotson

doi:10.1097/FPC.0b013e32833efb36

Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy

Gillian Smith, Simone Weidlich, Robert S. Dawe, Sally H. Ibbotson

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Objectives Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis.

Methods We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256).

Results We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [chi(2)(2 d.f.) = 8.862, P = 0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates.

Conclusion GSTM1 genotype may have clinical utility in the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects. Pharmacogenetics and Genomics 21: 217-224 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Original language	English
Pages (from-to)	217-224
Number of pages	8
Journal	Pharmacogenetics and Genomics
Volume	21
Issue number	4
DOIs	https://doi.org/10.1097/FPC.0b013e32833efb36
Publication status	Published - Apr 2011

Keywords

erythema
genotype
GSTM1
GSTT1
MC1R
phototherapy
polymorphism
TL-01
ultraviolet radiation
NONMELANOMA SKIN-CANCER
ULTRAVIOLET-B PHOTOTHERAPY
CUTANEOUS MALIGNANT-MELANOMA
RENAL-TRANSPLANT RECIPIENTS
POLYMERASE-CHAIN-REACTION
CHRONIC PLAQUE PSORIASIS
BASAL-CELL CARCINOMAS
GENE POLYMORPHISMS
DNA-DAMAGE
MELANOCORTIN-1 RECEPTOR

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/FPC.0b013e32833efb36

https://journals.lww.com/jpharmacogenetics/pages/articleviewer.aspx?year=2011&issue=04000&article=00007&type=abstractLicence: No Licence / Unknown

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@article{f4ca8b52ea2341468a676cae80d74499,

title = "Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy",

abstract = "Objectives Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis.Methods We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256).Results We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [chi(2)(2 d.f.) = 8.862, P = 0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates.Conclusion GSTM1 genotype may have clinical utility in the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects. Pharmacogenetics and Genomics 21: 217-224 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.",

keywords = "erythema, genotype, GSTM1, GSTT1, MC1R, phototherapy, polymorphism, TL-01, ultraviolet radiation, NONMELANOMA SKIN-CANCER, ULTRAVIOLET-B PHOTOTHERAPY, CUTANEOUS MALIGNANT-MELANOMA, RENAL-TRANSPLANT RECIPIENTS, POLYMERASE-CHAIN-REACTION, CHRONIC PLAQUE PSORIASIS, BASAL-CELL CARCINOMAS, GENE POLYMORPHISMS, DNA-DAMAGE, MELANOCORTIN-1 RECEPTOR",

author = "Gillian Smith and Simone Weidlich and Dawe, {Robert S.} and Ibbotson, {Sally H.}",

year = "2011",

month = apr,

doi = "10.1097/FPC.0b013e32833efb36",

language = "English",

volume = "21",

pages = "217--224",

journal = "Pharmacogenetics and Genomics",

issn = "1744-6872",

publisher = "Lippincott Williams and Wilkins",

number = "4",

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TY - JOUR

T1 - Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy

AU - Smith, Gillian

AU - Weidlich, Simone

AU - Dawe, Robert S.

AU - Ibbotson, Sally H.

PY - 2011/4

Y1 - 2011/4

N2 - Objectives Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis.Methods We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256).Results We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [chi(2)(2 d.f.) = 8.862, P = 0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates.Conclusion GSTM1 genotype may have clinical utility in the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects. Pharmacogenetics and Genomics 21: 217-224 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

AB - Objectives Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis.Methods We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256).Results We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [chi(2)(2 d.f.) = 8.862, P = 0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates.Conclusion GSTM1 genotype may have clinical utility in the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects. Pharmacogenetics and Genomics 21: 217-224 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

KW - erythema

KW - genotype

KW - GSTM1

KW - GSTT1

KW - MC1R

KW - phototherapy

KW - polymorphism

KW - TL-01

KW - ultraviolet radiation

KW - NONMELANOMA SKIN-CANCER

KW - ULTRAVIOLET-B PHOTOTHERAPY

KW - CUTANEOUS MALIGNANT-MELANOMA

KW - RENAL-TRANSPLANT RECIPIENTS

KW - POLYMERASE-CHAIN-REACTION

KW - CHRONIC PLAQUE PSORIASIS

KW - BASAL-CELL CARCINOMAS

KW - GENE POLYMORPHISMS

KW - DNA-DAMAGE

KW - MELANOCORTIN-1 RECEPTOR

U2 - 10.1097/FPC.0b013e32833efb36

DO - 10.1097/FPC.0b013e32833efb36

M3 - Article

C2 - 20802377

SN - 1744-6872

VL - 21

SP - 217

EP - 224

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

IS - 4

ER -

Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy

Abstract

Keywords

UN SDGs

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