title: Determination of DPYD enzyme activity in Korean population.
abstract: BACKGROUND
  Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil. This study was performed to analyze the association between DPYD genetic variants and DPYD enzyme activity in the Korean population.
  
  
  METHODS
  We screened the genetic variants and analyzed the enzyme activity in 73 healthy Korean subjects (69 men and 4 women; mean age, 22.6 years). Direct sequencing was conducted using the ABI 3730XL system, and enzyme activity was determined using high-performance liquid chromatography.
  
  
  RESULTS
  A total of 83 genetic variants were observed. Among the identified genetic variants, 32 were polymorphic including 3 core and 11 novel genetic variants. Association analysis between each genetic variant and enzyme activity in Korean subjects showed that 2 novel genetic variants, -832 G>A and -131 C>A, induced a significant difference in enzyme activity (P < 0.05).
  
  
  CONCLUSIONS
  To our knowledge, this is the first study that has examined the association between enzyme activity and DPYD genetic variants in the Korean population. In this study, we identified novel genetic variants that are associated with the enzyme activity. These findings will be valuable for further pharmacogenetic studies and especially useful for personalized medicine.
authors.affiliation: *Department of Life Science, Sogang University, Seoul; †Division of Clinical Research, Department of Toxicological Evaluation and Research, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do; and ‡Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Korea.
authors.forename: Joong-Gon
authors.initials: JG
authors.lastname: Shin
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Kang
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Na
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Myeon Woo
authors.initials: MW
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism*; D044466:Asian People / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil