Biol. Pharm. Bull. 28(11) 2117—2119 (2005)

methylation in azathioprine (AZA), thioguanine and 6-mercaptopurine (6-MP). The low TPMT activity in erythrocytes has been associated with an increased risk of severe and potentially fatal hematopoietic toxicity caused by the accumulation of the cytotoxic metabolites of thiopurine drugs. Genetic polymorphism of the TPMT activity in human was first reported by Weinshilboum and Sladek. Four variant TPMT alleles, TPMT*2 (G238C), TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G), were detected in over 80% of Caucasian individuals with intermediate metabolizers or poor metabolizers. The TPMT activity of one subject with TPMT*1/*3C was 40% lower than the mean value of TPMT activities in 44 Japanese subject. In the yeast expression system, TPMT activities of TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C mutant alleles showed 1.4—100 fold lower than that with the wild-type, respectively. These results suggested that the genetic polymorphism is a major determinant of the TPMT activity. On the other hand, Decaux et al. measured significantly lower TPMT activity in 53 women with SLE when compared with 30 healthy control participants but not with 28 patients with other dysimmune diseases. The allele frequency of TPMT mutation in SLE patients however, have not been reported in any of the TPMT pharmacogenetic studies. Based upon the background knowledge as discussed above, we intended to assess the genotype status of TPMT in a group of Japanese SLE patients who may undergo a therapy of AZA, a substrate drug, toward TPMT.