Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age

Hisato Suzuki, Hiroko Fukushima, Ryoko Suzuki, Sho Hosaka, Yuni Yamaki, Chie Kobayashi, Aiko Sakai, Kazuo Imagawa, Atsushi Iwabuchi, Ai Yoshimi, Tomohei Nakao, Keisuke Kato, Masahiro Tsuchida, Nobutaka Kiyokawa, Kazutoshi Koike, Emiko Noguchi, Takashi Fukushima, Ryo Sumazaki

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.

Original languageEnglish
Pages (from-to)797-801
Number of pages5
JournalJournal of Human Genetics
Volume61
Issue number9
DOIs
Publication statusPublished - 2016 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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