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

Richard Warren, Richard B. Warren, Rhodri Ll Smith, Emanuela Campalani, Steve Eyre, Catherine H. Smith, Jonathan N W N Barker, Jane Worthington, Christopher E M Griffiths

    Research output: Contribution to journalArticlepeer-review

    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. © 2008 The Society for Investigative Dermatology.
    Original languageEnglish
    Pages (from-to)1925-1929
    Number of pages4
    JournalJournal of Investigative Dermatology
    Volume128
    Issue number8
    DOIs
    Publication statusPublished - Aug 2008

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