ASIA unversity:Item 310904400/2466
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    题名: Detecting the frequencies of inosine triphosphate pyrophosphatase gene polymorphisms in Taiwan.
    作者: shao-huan lan
    贡献者: Department of Biotechnology
    关键词: ITPA;TPMT;polymorphism;thiopurine;AZA
    日期: 2005
    上传时间: 2009-11-06 06:09:47 (UTC+0)
    出版者: Asia University
    摘要: Drug adverse reaction from azathioprine treatment affects up to 37% of patients. Thiopurine methyltransferase (TPMT) polymorphisms will prospectively identify approximately 10% of patients. Recently, a polymorphism in the inosine triphosphate pyrophosphatase gene (ITPA) has been associated with severe azathioprine toxicity. The enzyme inosine triphosphate pyrophosphatase catalyses the pyrophosphohydrolysis of ITP to IMP. Inosine triphosphate pyrophosphohydrolase deficiency is a common inherited condition characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes. A deficiency of ITPase may occur adverse reactions to therapy with the thiopurine drug 6-mercaptopurine (6-MP) and its prodrug azathioprine. The genetic basis and pathological mechanism of ITPase deficiency are unknown. Below have characterized the genomic structure of the ITPA gene, showing that it has eight exons. Five single nucleotide polymorphisms (SNP) were identified, three silent (138G-->A, 561G-->A, 708G-->A) and two associated with ITPase deficiency (94C-->A, IVS2+21A-->C).In this study, we examine the frequencies of ITPA polymorphisms in 100 healthy taiwanese individuals. The allele frequency of the 94C > A variant in the Taiwnese sample was 0.17 (Caucasian allele frequency 0.06).The IV2 + 21A > C polymorphism was 0 (Caucasian allele frequency 0.130). Allele frequencies of the 138G > A, 561G > A and 708G > A polymorphisms were 0.395, 0.47 and 0.16 respectively in the Taiwanese population, and with the exception of the 138G > A polymorphism, this study reveal that Taiwanese allele frequencies is higher than Caucasians. This data provides a foundation on which prospective studies can be planned to identify patients at risk for severe toxicity from azathioprine therapy.
    显示于类别:[生物科技學系] 博碩士論文

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