Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi Hachioji, Tokyo, 192-0392 Japan.
Genome Med. 2009 Dec 29;1(12):118. doi: 10.1186/gm118.
Many factors, including genetic components and acquired factors such as obesity and alcohol consumption, influence serum uric acid (urate) concentrations. Since serum urate concentrations are determined by the balance between renal urate excretion and the volume of urate produced via purine metabolism, urate transporter genes as well as genes coding for enzymes involved in purine metabolism affect serum urate concentrations. URAT1 was the first transporter affecting serum urate concentrations to be identified. Using the characterization of this transporter as an indicator, several transporters have been shown to transport urate, allowing the construction of a synoptic renal urate transport model. Notable re-absorptive urate transporters are URAT1 at apical membranes and GLUT9 at basolateral membranes, while ABCG2, MRP4 (multidrug resistance protein 4) and NPT1 are secretive transporters at apical membranes. Recent genome-wide association studies have led to validation of the in vitro model constructed from each functional analysis of urate transporters, and identification of novel candidate genes related to urate metabolism and transport proteins, such as glucokinase regulatory protein (GKRP), PDZK1 and MCT9. However, the function and physiologic roles of several candidates, as well as the influence of acquired factors such as obesity, foods, or alcoholic beverages, remain unclear.
许多因素，包括遗传成分和后天因素如肥胖和饮酒，都会影响血清尿酸（尿酸）浓度。由于血清尿酸浓度取决于肾脏尿酸排泄和嘌呤代谢产生的尿酸量之间的平衡，尿酸转运蛋白基因以及编码参与嘌呤代谢的酶的基因会影响血清尿酸浓度。URAT1 是第一个被确定影响血清尿酸浓度的转运蛋白。利用该转运蛋白的特性作为指标，已经发现了几种转运蛋白可以转运尿酸，从而构建了一个综合的肾脏尿酸转运模型。值得注意的是，尿酸的重吸收转运蛋白是顶端膜上的 URAT1 和基底外侧膜上的 GLUT9，而 ABCG2、MRP4（多药耐药蛋白 4）和 NPT1 是顶端膜上的分泌性转运蛋白。最近的全基因组关联研究验证了从尿酸转运蛋白的每种功能分析构建的体外模型，并鉴定出与尿酸代谢和转运蛋白相关的新候选基因，如葡萄糖激酶调节蛋白（GKRP）、PDZK1 和 MCT9。然而，一些候选基因的功能和生理作用，以及肥胖等后天因素、食物或酒精饮料的影响，仍不清楚。
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