Pharmacogenetic significance of inosine triphosphatase

被引:77
作者
Bierau, Jorgen [1 ]
Lindhout, Martijn [1 ]
Bakker, Jaap A. [1 ]
机构
[1] Maastricht Univ Hosp, Lab Biochem Genet, Dept Clin Genet, Maastricht, Netherlands
关键词
adverse drug; reactions; allelic variant; azathioprine; inborn error of; metabolism; inosine; triphosphatase; triphosphate; pyrophosphohydrolase; mercaptopurine; pharmacogenetics; thiopurine; thiopurine methyltransferase;
D O I
10.2217/14622416.8.9.1221
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Inosine triphosphatase (ITPase) is the enzyme that catalyzes the conversion of inosine triphosphate (ITP) and deoxy-inosine triphosphate (dITP) to inosine monophosphate and deoxy-inosine monophosphate, respectively, thereby maintaining low intracellular concentrations of ITP and dITR Individuals deficient in ITPase activity were first recognized over 30 years ago. For decades, no clinical significance could be attributed to this inborn error of metabolism whatsoever. In recent years, evidence has started to accumulate that polymorphisms in the gene encoding ITPase are associated with potentially severe adverse drug reactions towards the thiopurine drugs azathioprine and 6-mercaptopurine. The pharmacogenetic significance is presently being debated in the literature. However, the present state of knowledge is still insufficient to definitively determine the pharmacogenetic significance of ITPase. This article aims to review the current knowledge on the role of ITPase in thiopurine metabolism.
引用
收藏
页码:1221 / 1228
页数:8
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