Hyperuricaemia: contributions of urate transporter ABCG2 and the fractional renal clearance of urate.

Abstract:

OBJECTIVE:To investigate the contributions towards hyperuricaemia of known risk factors, focusing on fractional (renal) clearance of urate (FCU) and variation in the ATP-binding cassette transporter, sub-family G 2 (ABCG2) gene. METHODS:The contributions of age, sex, ancestry, Q141K genotype for ABCG2, FCU, sugar-sweetened beverage and alcohol consumption, metabolic syndrome disorders and measures of renal function to the risk of hyperuricaemia were evaluated by comparing hyperuricaemic (serum urate≥0.42 mmol/L, n=448) with normouricaemic (serum urate<0.42 mmol/L, n=344) participants using stepwise logistic regression. Model performance was evaluated using the area under the receiver operator characteristic curve (AUROC). RESULTS:ABCG2 genotype, FCU, male sex, body mass index, serum triglyceride concentrations, estimated glomerular filtration rate and consumption of alcohol were the best predictors of hyperuricaemia (AUROC 0.90, 81% accuracy). Homozygosity in the 141K variant for ABCG2 conferred an adjusted OR of 10.5 for hyperuricaemia (95% CI 2.4 to 46.2). For each 1% decrease of FCU, the adjusted OR increased by 51% (OR 1.51, 95% CI 1.37 to 1.66). There was no association between ABCG2 genotype and FCU (r=0.02, p=0.83). CONCLUSIONS:The ABCG2 141K variant and the FCU contribute strongly but independently to hyperuricaemia. These findings provide further evidence for a significant contribution of ABCG2 to extra-renal (gut) clearance of urate.

journal_name

Ann Rheum Dis

authors

Kannangara DR,Phipps-Green AJ,Dalbeth N,Stamp LK,Williams KM,Graham GG,Day RO,Merriman TR

doi

10.1136/annrheumdis-2015-208111

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

1363-6

issue

7

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2015-208111

journal_volume

75

pub_type

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