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 TPMT1/3, 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 TPMT1/3C (20.3 +/- 8.1 pmol/h/mgHb) was 25% lower than that in 151 subjects with TPMT1/1 (27.0 +/- 5.1 pmol/h/mgHb), there was overlap. The ranges of TPMT activity in subjects with TPMT1/1 and those with TPMT1/3C were similar. The median values in TPMT1/3C and TPMT1/*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.