Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasisCitation formats

  • External authors:
  • Richard B. Warren
  • Rhodri Ll Smith
  • Emanuela Campalani
  • Catherine H. Smith
  • Jonathan N W N Barker

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Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. / Warren, Richard; Warren, Richard B.; Smith, Rhodri Ll; Campalani, Emanuela; Eyre, Steve; Smith, Catherine H.; Barker, Jonathan N W N; Worthington, Jane; Griffiths, Christopher E M.

In: Journal of Investigative Dermatology, Vol. 128, No. 8, 08.2008, p. 1925-1929.

Research output: Contribution to journalArticle

Harvard

Warren, R, Warren, RB, Smith, RL, Campalani, E, Eyre, S, Smith, CH, Barker, JNWN, Worthington, J & Griffiths, CEM 2008, 'Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis', Journal of Investigative Dermatology, vol. 128, no. 8, pp. 1925-1929. https://doi.org/10.1038/jid.2008.16

APA

Vancouver

Warren R, Warren RB, Smith RL, Campalani E, Eyre S, Smith CH et al. Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. Journal of Investigative Dermatology. 2008 Aug;128(8):1925-1929. https://doi.org/10.1038/jid.2008.16

Author

Warren, Richard ; Warren, Richard B. ; Smith, Rhodri Ll ; Campalani, Emanuela ; Eyre, Steve ; Smith, Catherine H. ; Barker, Jonathan N W N ; Worthington, Jane ; Griffiths, Christopher E M. / Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. In: Journal of Investigative Dermatology. 2008 ; Vol. 128, No. 8. pp. 1925-1929.

Bibtex

@article{2f16584824ef40a083517b95af6ec56c,
title = "Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis",
abstract = "Methotrexate, an inexpensive first-line systemic therapy for moderate-to-severe psoriasis, is limited in its use by unpredictable efficacy and toxicity. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in methotrexate transmembrane transporters and adenosine receptors are associated with efficacy and/or toxicity of the drug. DNA was collected from 374 patients with chronic plaque psoriasis who had been treated with methotrexate. Phenotypic data on efficacy and toxicity were available. Haplotype tagging SNPs (r2>0.8) across the relevant genes, with a minor allele frequency of >5{\%}, were selected from the HAPMAP phase II data. SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity. With one SNP in ABCC1, rs246240, the carriage of two copies of allele 1 gives an odds ratio of 2.2 (95{\%} confidence interval: 1.3-3.6; P=0.001) for developing toxicity to methotrexate. These data indicate that knowledge of SNPs in genes relevant to methotrexate efflux may be important in selecting patients suitable for this therapy. {\circledC} 2008 The Society for Investigative Dermatology.",
author = "Richard Warren and Warren, {Richard B.} and Smith, {Rhodri Ll} and Emanuela Campalani and Steve Eyre and Smith, {Catherine H.} and Barker, {Jonathan N W N} and Jane Worthington and Griffiths, {Christopher E M}",
year = "2008",
month = "8",
doi = "10.1038/jid.2008.16",
language = "English",
volume = "128",
pages = "1925--1929",
journal = "The Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Springer Nature",
number = "8",

}

RIS

TY - JOUR

T1 - Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis

AU - Warren, Richard

AU - Warren, Richard B.

AU - Smith, Rhodri Ll

AU - Campalani, Emanuela

AU - Eyre, Steve

AU - Smith, Catherine H.

AU - Barker, Jonathan N W N

AU - Worthington, Jane

AU - Griffiths, Christopher E M

PY - 2008/8

Y1 - 2008/8

N2 - Methotrexate, an inexpensive first-line systemic therapy for moderate-to-severe psoriasis, is limited in its use by unpredictable efficacy and toxicity. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in methotrexate transmembrane transporters and adenosine receptors are associated with efficacy and/or toxicity of the drug. DNA was collected from 374 patients with chronic plaque psoriasis who had been treated with methotrexate. Phenotypic data on efficacy and toxicity were available. Haplotype tagging SNPs (r2>0.8) across the relevant genes, with a minor allele frequency of >5%, were selected from the HAPMAP phase II data. SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity. With one SNP in ABCC1, rs246240, the carriage of two copies of allele 1 gives an odds ratio of 2.2 (95% confidence interval: 1.3-3.6; P=0.001) for developing toxicity to methotrexate. These data indicate that knowledge of SNPs in genes relevant to methotrexate efflux may be important in selecting patients suitable for this therapy. © 2008 The Society for Investigative Dermatology.

AB - Methotrexate, an inexpensive first-line systemic therapy for moderate-to-severe psoriasis, is limited in its use by unpredictable efficacy and toxicity. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in methotrexate transmembrane transporters and adenosine receptors are associated with efficacy and/or toxicity of the drug. DNA was collected from 374 patients with chronic plaque psoriasis who had been treated with methotrexate. Phenotypic data on efficacy and toxicity were available. Haplotype tagging SNPs (r2>0.8) across the relevant genes, with a minor allele frequency of >5%, were selected from the HAPMAP phase II data. SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity. With one SNP in ABCC1, rs246240, the carriage of two copies of allele 1 gives an odds ratio of 2.2 (95% confidence interval: 1.3-3.6; P=0.001) for developing toxicity to methotrexate. These data indicate that knowledge of SNPs in genes relevant to methotrexate efflux may be important in selecting patients suitable for this therapy. © 2008 The Society for Investigative Dermatology.

U2 - 10.1038/jid.2008.16

DO - 10.1038/jid.2008.16

M3 - Article

VL - 128

SP - 1925

EP - 1929

JO - The Journal of Investigative Dermatology

JF - The Journal of Investigative Dermatology

SN - 0022-202X

IS - 8

ER -