title: Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population.
abstract: Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. The molecular basis for the genetic polymorphism of TPMT has been established for European Caucasians, African-Americans, Southwest Asians and Chinese, but it remains to be elucidated in Japanese populations. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G) were determined in Japanese samples (n=192) using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. TPMT*3C was found in 0.8% of the samples (three heterozygotes). The TPMT*2, TPMT*3A and TPMT*3B alleles were not detected in any of the samples analyzed. This study provides the first analysis of TPMT mutant allele frequency in a sample of Japanese population and indicates that TPMT*3C is the most common allele in Japanese subjects.
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hiratsuka
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: F
authors.initials: F
authors.lastname: Omori
authors.forename: Y
authors.initials: Y
authors.lastname: Agatsuma
authors.forename: M
authors.initials: M
authors.lastname: Mizugaki
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D005828:Genetics, Population; D006801:Humans; D007564:Japan; D008780:Methyltransferases / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase