Frequency distribution of thiopurine S-methyltransferase activity in red blood cells of a healthy Japanese population.
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.
Kubota
Takahiro
T
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Tokyo, Japan. tkubota-tky@umin.ac.jp
Nishida
Akihito
A
Takeuchi
Ken
K
Iida
Takayuki
T
Yokota
Hiromitsu
H
Higashi
Katsumi
K
Nakahara
Kazuhiko
K
Hanai
Hiroyuki
H
Iga
Tatsuji
T
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
D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase