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ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout

The Pharmacogenomics Journal volume 17, pages 201–203 (2017)Cite this article

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Abstract

Many patients fail to achieve the recommended serum urate (SU) target (<6 mgdl−1) with allopurinol. The aim of our study was to examine the association of ABCG2 with SU target in response to standard doses of allopurinol using a cohort with confirmed adherence. Good response was defined as SU<6 mgdl−1 on allopurinol ⩽300 mgd−1 and poor response as SU⩾6 mgdl−1 despite allopurinol >300 mgd−1. Adherence was confirmed by oxypurinol concentrations. ABCG2 genotyping was performed using pre-designed single nucleotide polymorphism (SNP) TaqMan assays. Of 264 patients, 120 were good responders, 68 were poor responders and 76 were either non-adherent or could not be classified. The minor allele of ABCG2 SNP rs2231142 conferred a significantly increased risk of poor response to allopurinol (odds ratio=2.71 (1.70–4.48), P=6.0 × 10−5). This association remained significant after adjustment for age, sex, body mass index, ethnicity, estimated glomerular filtration rate, diuretic use and SU off urate-lowering therapy. ABCG2 rs2231142 predicts poor response to allopurinol, as defined by SU⩾6 mgdl−1 despite allopurinol >300 mgd−1.

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Acknowledgements

We thank the patients for generously giving their time to participate in this study. Financial support for this study was provided by project and programme grants from the Health Research Council of New Zealand.

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Authors and Affiliations

  1. Department of Surgical Sciences, Dunedin School of Medicine, Dunedin, New Zealand

    R L Roberts & M C Wallace

  2. Department of Biochemistry, University of Otago, Dunedin, New Zealand

    A J Phipps-Green, R Topless & T R Merriman

  3. Department of Medicine, University of Otago, Christchurch, New Zealand

    J M Drake & L K Stamp

  4. Department of Medicine, University of Auckland, Auckland, New Zealand

    P Tan & N Dalbeth

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  1. R L Roberts
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  2. M C Wallace
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  3. A J Phipps-Green
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  4. R Topless
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  7. N Dalbeth
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  8. T R Merriman
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  9. L K Stamp
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Correspondence to L K Stamp.

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Competing interests

Dalbeth, Stamp, Merriman and Roberts report grants from the Health Research Council of New Zealand, during the conduct of the study and from Ardea Biosciences for related work that is not part of this manuscript. Dalbeth reports personal fees from Takeda, Teijin, Menarini, Pfizer and Cymabay, grants and personal fees from AstraZeneca, Ardea Biosciences and Fonterra, outside the submitted work. In addition, Dalbeth has a patent Milk Products for Gout pending. Stamp reports consulting fees from Astra Zeneca unrelated to the submitted work.

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Roberts, R., Wallace, M., Phipps-Green, A. et al. ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. Pharmacogenomics J 17, 201–203 (2017). https://doi.org/10.1038/tpj.2015.101

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  • DOI: https://doi.org/10.1038/tpj.2015.101

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