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ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout.
Pharmacogenomics J. 2017 03; 17(2):201-203.PJ

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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Publisher Full Text (DOI)

Authors+Show Affiliations

Roberts RL
Department of Surgical Sciences, Dunedin School of Medicine, Dunedin, New Zealand.
Wallace MC
Department of Surgical Sciences, Dunedin School of Medicine, Dunedin, New Zealand.
Phipps-Green AJ
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Topless R
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Drake JM
Department of Medicine, University of Otago, Christchurch, New Zealand.
Tan P
Department of Medicine, University of Auckland, Auckland, New Zealand.
Dalbeth N
Department of Medicine, University of Auckland, Auckland, New Zealand.
Merriman TR
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Stamp LK
Department of Medicine, University of Otago, Christchurch, New Zealand.

MeSH

ATP Binding Cassette Transporter, Subfamily G, Member 2AdultAgedAged, 80 and overAllopurinolBiomarkersFemaleGene FrequencyGenotypeGoutGout SuppressantsHumansLogistic ModelsMaleMiddle AgedNeoplasm ProteinsOdds RatioOxypurinolPharmacogeneticsPharmacogenomic VariantsPhenotypePolymorphism, Single NucleotideRisk FactorsTreatment OutcomeUric AcidYoung Adult

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26810134

Citation

Roberts, R L., et al. "ABCG2 Loss-of-function Polymorphism Predicts Poor Response to Allopurinol in Patients With Gout." The Pharmacogenomics Journal, vol. 17, no. 2, 2017, pp. 201-203.
Roberts RL, Wallace MC, Phipps-Green AJ, et al. ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. Pharmacogenomics J. 2017;17(2):201-203.
Roberts, R. L., Wallace, M. C., Phipps-Green, A. J., Topless, R., Drake, J. M., Tan, P., Dalbeth, N., Merriman, T. R., & Stamp, L. K. (2017). ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. The Pharmacogenomics Journal, 17(2), 201-203. https://doi.org/10.1038/tpj.2015.101
Roberts RL, et al. ABCG2 Loss-of-function Polymorphism Predicts Poor Response to Allopurinol in Patients With Gout. Pharmacogenomics J. 2017;17(2):201-203. PubMed PMID: 26810134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. AU - Roberts,R L, AU - Wallace,M C, AU - Phipps-Green,A J, AU - Topless,R, AU - Drake,J M, AU - Tan,P, AU - Dalbeth,N, AU - Merriman,T R, AU - Stamp,L K, Y1 - 2016/01/26/ PY - 2015/08/12/received PY - 2015/10/19/revised PY - 2015/11/16/accepted PY - 2016/1/27/pubmed PY - 2017/8/9/medline PY - 2016/1/27/entrez SP - 201 EP - 203 JF - The pharmacogenomics journal JO - Pharmacogenomics J VL - 17 IS - 2 N2 - 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. SN - 1473-1150 UR - https://www.unboundmedicine.com/medline/citation/26810134/ABCG2_loss_of_function_polymorphism_predicts_poor_response_to_allopurinol_in_patients_with_gout_ DB - PRIME DP - Unbound Medicine ER -