Identification of urate transporter, genetic analysis of renal hypouricemia and the development of anti-hyperuricemia drug

我们已经成功地克隆了urate transporter （URAT 1），这是在人类肾脏的管子中重新吸收的，并演示了transcript蛋白显示了urate transport的功能（Nature 417（6887）：447-452，2002）。我们生产的抗体对抗蛋白质，并证明蛋白质表现在再生管中。与renal hypouricemia展示了URAT 1基因的同源突变，而URAT 1对renal hypouricemia是一种基因反应。This gene is a target molecule for the Management of anti-hyperuricemia drugs。We studed the association between single nucleotide polymorphism（SNP） mutation of URAT1 and the serum levels of urate。We？zed mutations of URAT1 [Ex3（C217;Thr ￣ Met） （C ￣ T）和Ex4（G258 A;Trp ￣ stop）（G ￣ A）] by using Light-Cycler in 164 healthy subjects who had taken health checkup at our hospital。We found that for Ex3 mutation（C217;Thr→Met）（C→T）， one subject showed hetero mutation， and none showed homo mutation， and that for Ex4（G258A;Trp→stop）（G→A）， 3 subject showed hetero mutation， and none showed homo mutation。异源突变的血清水平为4.1 mg/dl，E4突变为5.3 mg/dl， 4.2 mg/dl，4.5 mg/dl。因此，URAT 1的异质突变与高种族灭绝不相关。

We have succeeded in cloning of urate transporter (URAT1) that is involved in the reabsorption of urate in the tubules of human kidneys, and demonstrated that the transcript protein shows the function of urate transport (Nature 417(6887):447-452,2002). We produced antibody against the protein, and demonstrated that the protein is expressed in the renal tubules. Patients with renal hypouricemia showed homo mutation in the gene of URAT1,and thus URAT1 is a gene responsible for renal hypouricemia. This gene is a target molecule for the development of anti-hyperuricemia drugs.We studied the association between single nucleotide polymorphism(SNP) mutation of URAT1 and the serum levels of urate. We analyzed mutations of URAT1 [Ex3(C217;Thr→Met) (C→T)とEx4(G258A;Trp→stop)(G→A)] by using Light-Cycler in 164 healthy subjects who had taken health checkup at our hospital. We found that for Ex3 mutation(C217;Thr→Met)(C→T), one subject showed hetero mutation, and none showed homo mutation, and that for Ex4(G258A;Trp→stop)(G→A), 3 subjects showed hetero mutation, and none showed homo mutation. The serum levels of urate in the subjects with hetero mutation were 4.1 mg/dl for Ex3 mutation, and 5.3 mg/dl, 4.2 mg/dl, and 4.5 mg/dl for E4 mutation. Thus, the hetero mutation of URAT1 was not associated with hypouricemia.