title: ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout.
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-1on allopurinol ⩽300 mgd-1and poor response as SU⩾6 mgdl-1despite 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-1despite allopurinol >300 mgd-1.
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, Dunedin, New Zealand.
authors.forename: R L
authors.initials: RL
authors.lastname: Roberts
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, Dunedin, New Zealand.
authors.forename: M C
authors.initials: MC
authors.lastname: Wallace
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: A J
authors.initials: AJ
authors.lastname: Phipps-Green
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Topless
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: J M
authors.initials: JM
authors.lastname: Drake
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: N
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: T R
authors.initials: TR
authors.lastname: Merriman
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: L K
authors.initials: LK
authors.lastname: Stamp
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000097:blood / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006073:Gout / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006074:Gout Suppressants / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016017:Odds Ratio; D010117:Oxypurinol / Q000097:blood; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D015415:Biomarkers; D006074:Gout Suppressants; D009363:Neoplasm Proteins; D014527:Uric Acid; D000493:Allopurinol; D010117:Oxypurinol
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