title: Detection assay of rare variants of the thiopurine methyltransferase gene by PCR-RFLP using a mismatch primer in a Japanese population.
abstract: Thiopurine methyltransferase (TPMT) catalyzes the metabolism of important drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. The identification and frequency distributions of several variant TPMT alleles (TPMT*2--*8) have been described recently in many ethnic groups. We have recently demonstrated that TPMT*3C is the most common allele in Japanese subjects; however, it remains to be elucidated whether TPMT*4--*8 variants also exist in Japanese subjects. To detect polymorphisms in the TPMT gene (TPMT*4--*8), we have developed a mismatch polymerase chain reaction and restriction fragment length polymorphism method and conducted a population study of Japanese subjects. Genotyping of these variant forms was carried out in 192 Japanese healthy volunteers. The TPMT*4, TPMT*5, TPMT*6, TPMT*7, and TPMT*8 variants were not detected in any of the samples analyzed. This study provides the first analysis of the TPMT*4--*8 variants in a sample of the Japanese population and indicates that TPMT*4--*8 variants do not occur or are rare alleles in this population.
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital, 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: Y
authors.initials: Y
authors.lastname: Kishikawa
authors.forename: M
authors.initials: M
authors.lastname: Mizugaki
mesh_terms: D000483:Alleles; D005838:Genotype; D006801:Humans; D007564:Japan; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase