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

点击翻译按钮获取中文摘要

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.