TY - JOUR
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
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ymgme.2005.03.011
DO - 10.1016/j.ymgme.2005.03.011
M3 - Article
C2 - 15946879
AN - SCOPUS:23044444317
SN - 1096-7192
VL - 85
SP - 271
EP - 279
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 4
ER -