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

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 mgdl(-1) and poor response as SU >= 6 mgdl-(1) despite allopurinol >300 mgdl(-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 x 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).