Novel single nucleotide polymorphisms of the dihydropyrimidinase gene (DPYS) in Japanese individuals

Fumika Akai; Hiroki Hosono; Noriyasu Hirasawa; Masahiro Hiratsuka

doi:10.1016/j.dmpk.2014.09.005

Novel single nucleotide polymorphisms of the dihydropyrimidinase gene (DPYS) in Japanese individuals

Drug Metab Pharmacokinet. 2015 Feb;30(1):127-9. doi: 10.1016/j.dmpk.2014.09.005. Epub 2014 Sep 28.

Authors

Fumika Akai¹, Hiroki Hosono¹, Noriyasu Hirasawa¹, Masahiro Hiratsuka²

Affiliations

¹ Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
² Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: mhira@m.tohoku.ac.jp.

PMID: 25760541
DOI: 10.1016/j.dmpk.2014.09.005

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.

Keywords: DPYS; Dihydropyrimidinase; Genetic polymorphism; Japanese; SNP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases / genetics*
Asian People / genetics*
Exons / genetics
Fluorouracil / metabolism
Genetics, Population
Healthy Volunteers
Humans
Introns / genetics
Japan
Polymorphism, Single Nucleotide*

Substances

Amidohydrolases
dihydropyrimidinase
Fluorouracil