title: Frequency distribution of thiopurine S-methyltransferase activity in red blood cells of a healthy Japanese population.
abstract: Thiopurine S-methyltransferase (TPMT), which exhibits a genetic polymorphism, plays an important role in the metabolism of thiopurine drugs such as mercaptopurine, thioguanine, and azathioprine. To determine the frequency distribution of TPMT activity in 157 Japanese subjects with different TPMT genotypes, ie, TPMT*1/*1 and TPMT*1/*3, the authors measured levels of 6-methylmercaptopurine formed from 6-mercaptopurine in red blood cells lysates by HPLC. The TPMT activities in our Japanese subjects ranged from 11.0 to 42.6 pmol/h/mgHb. Although the mean value of TPMT activities in 6 subjects with TPMT*1/*3C (20.3 +/- 8.1 pmol/h/mgHb) was 25% lower than that in 151 subjects with TPMT*1/*1 (27.0 +/- 5.1 pmol/h/mgHb), there was overlap. The ranges of TPMT activity in subjects with TPMT*1/*1 and those with TPMT*1/*3C were similar. The median values in TPMT*1/*3C and TPMT*1/*1 individuals were 20.1 (11.0-31.2) and 26.8 pmol/h/mgHb (15.7-42.7), respectively (Mann-Whitney U-test: median difference 6.7 pmol/h/mgHb, 95% CI 0-25.5, P < 0.05). This observation may have relevance for the use of 6-mercaptopurine and azathioprine as therapeutic agents in Japanese patients.
authors.affiliation: Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Tokyo, Japan. tkubota-tky@umin.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kubota
authors.forename: Akihito
authors.initials: A
authors.lastname: Nishida
authors.forename: Ken
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iida
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yokota
authors.forename: Katsumi
authors.initials: K
authors.lastname: Higashi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hanai
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Iga
mesh_terms: D044466:Asian People; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D007564:Japan; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase