title: Novel single nucleotide polymorphisms of the dihydropyrimidinase gene (DPYS) in Japanese individuals.
abstract: Genetic polymorphisms of the dihydropyrimidinase gene (DPYS) may be associated with the development of severe toxicity to 5-fluorouracil, a drug used to treat solid tumors. In this study, we analyzed the nine coding exons and exon-intron junctions of DPYS in 183 Japanese individuals. We detected two novel single nucleotide polymorphisms (SNPs)-285C > T (Thr95Thr) and 349T > C (Trp117Arg)-in exon 2. The nonsynonymous SNP 349T > C was analyzed in 208 Japanese individuals. Although the allele frequency of the SNP in the Japanese population was found to be extremely low (0.13%), the enzymatic activity of the variant protein might be reduced compared with that of the wild-type protein.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Fumika
authors.initials: F
authors.lastname: Akai
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hosono
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: mhira@m.tohoku.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005472:Fluorouracil / Q000378:metabolism; D005828:Genetics, Population; D064368:Healthy Volunteers; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D020641:Polymorphism, Single Nucleotide
chemical_list: D000581:Amidohydrolases; C020047:dihydropyrimidinase; D005472:Fluorouracil
keywords: DPYS; Dihydropyrimidinase; Genetic polymorphism; Japanese; SNP