Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population

Tohru Maeda, Satoshi Sumi, Akihito Ueta, Yumiko Ohkubo, Tetsuya Ito, Anthony M. Marinaki, Yukihisa Kurono, Shinsaku Hasegawa, Hajime Togari

Research output: Contribution to journalArticle

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Abstract

Inosine triphosphate pyrophosphohydrolase (ITPase) is an enzyme that catalyzes the conversion of inosine triphosphate (ITP) to inosine monophosphate and pyrophosphate. In Caucasian populations it is reported that the frequency of cases showing decreased ITPase activity is 5%. The structure of ITPA gene along with five single nucleotide polymorphisms has been reported in Caucasians. We examined ITPase activity and frequency of two polymorphisms (94C > A and IVS2 + 21A > C) in 100 Japanese individuals. Among these individuals, we observed that three cases with zero activity were homozygote for 94C > A, and were accompanied by abnormal accumulation of ITP in erythrocytes. The cases included in the low ITPase activity group were heterozygote for 94C > A polymorphism. The activity of the heterozygote cases was approximately 27% of the mean value of the wild type. The allele frequency of the 94C > A polymorphism was 0.155, which was 2.6 times higher than that of the Caucasians (0.06). The IVS2 + 21A > C was not detected in Japanese cases, although it occurred with a frequency of 0.130 in Caucasians. Furthermore, we identified a novel mutation IVS2 + 68T > G in intron 2 in the case with the lowest enzyme activity in the 94C > A wild type. Since the frequency of ITPA 94C > A polymorphism is higher in the Japanese population than that in Caucasians, it is more important to examine ITPA 94C > A polymorphism in the Japanese population to prevent thiopurine drug toxicity. Pretherapeutic screening of individuals for ITPA polymorphisms should be considered for safer and more tolerable treatment with thiopurine drugs.

Original languageEnglish
Pages (from-to)271-279
Number of pages9
JournalMolecular Genetics and Metabolism
Volume85
Issue number4
DOIs
Publication statusPublished - 01-08-2005
Externally publishedYes

Fingerprint

Polymorphism
Inosine Triphosphate
Heterozygote
Population
Inosine Diphosphate
Inosine Monophosphate
Homozygote
Enzymes
Drug-Related Side Effects and Adverse Reactions
Gene Frequency
Introns
Single Nucleotide Polymorphism
Erythrocytes
Enzyme activity
Mutation
inosine triphosphatase
Pharmaceutical Preparations
Toxicity
Screening
Genes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Maeda, Tohru ; Sumi, Satoshi ; Ueta, Akihito ; Ohkubo, Yumiko ; Ito, Tetsuya ; Marinaki, Anthony M. ; Kurono, Yukihisa ; Hasegawa, Shinsaku ; Togari, Hajime. / Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population. In: Molecular Genetics and Metabolism. 2005 ; Vol. 85, No. 4. pp. 271-279.
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Maeda, T, Sumi, S, Ueta, A, Ohkubo, Y, Ito, T, Marinaki, AM, Kurono, Y, Hasegawa, S & Togari, H 2005, 'Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population', Molecular Genetics and Metabolism, vol. 85, no. 4, pp. 271-279. https://doi.org/10.1016/j.ymgme.2005.03.011

Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population. / Maeda, Tohru; Sumi, Satoshi; Ueta, Akihito; Ohkubo, Yumiko; Ito, Tetsuya; Marinaki, Anthony M.; Kurono, Yukihisa; Hasegawa, Shinsaku; Togari, Hajime.

In: Molecular Genetics and Metabolism, Vol. 85, No. 4, 01.08.2005, p. 271-279.

Research output: Contribution to journalArticle

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T1 - Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population

AU - Maeda, Tohru

AU - Sumi, Satoshi

AU - Ueta, Akihito

AU - Ohkubo, Yumiko

AU - Ito, Tetsuya

AU - Marinaki, Anthony M.

AU - Kurono, Yukihisa

AU - Hasegawa, Shinsaku

AU - Togari, Hajime

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