高尿酸血症：尿酸转运体 ABCG2 和尿酸的肾部分清除率的作用。

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

机构信息

School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.

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

出版信息

Ann Rheum Dis. 2016 Jul;75(7):1363-6. doi: 10.1136/annrheumdis-2015-208111. Epub 2015 Dec 1.

DOI:10.1136/annrheumdis-2015-208111

PMID:26835700

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.

摘要

目的

探讨已知危险因素对高尿酸血症的贡献，重点研究尿酸的分数（肾脏）清除率（FCU）和三磷酸腺苷结合盒转运体，G 家族 2 成员（ABCG2）基因的变异。

方法

通过比较高尿酸血症（血清尿酸≥0.42mmol/L，n=448）和正常尿酸血症（血清尿酸<0.42mmol/L，n=344）参与者，使用逐步逻辑回归评估年龄、性别、祖源、ABCG2 的 Q141K 基因型、FCU、含糖饮料和酒精摄入、代谢综合征紊乱以及肾功能指标对高尿酸血症的贡献。使用接收者操作特征曲线（AUROC）下面积评估模型性能。

结果

ABCG2 基因型、FCU、男性、体重指数、血清甘油三酯浓度、估计肾小球滤过率和酒精摄入是高尿酸血症的最佳预测因素（AUROC 0.90，81%准确性）。ABCG2 141K 变体的纯合性使高尿酸血症的调整后比值比增加了 10.5 倍（95%CI 2.4 至 46.2）。FCU 每降低 1%，调整后的比值比增加 51%（OR 1.51，95%CI 1.37 至 1.66）。ABCG2 基因型和 FCU 之间没有关联（r=0.02，p=0.83）。