title: Evaluation of dihydropyrimidine dehydrogenase activity in South-west Asian, Kenyan and Ghanaian populations.
abstract: OBJECTIVE
  Dihydropyrimidine dehydrogenase (DPD) reduces endogenous pyrimidines and therapeutic analogues such as the anticancer agent 5-fluorouracil (5FU). Among Caucasian populations DPD activity is highly variable and subject to polymorphic regulation. To evaluate interethnic influence, DPD activity was assessed in South-west Asian, Kenyan and Ghanaian populations.
  
  
  METHODS
  DPD activity was determined in peripheral mononuclear cells using[14C]-5-fluorouracil and h.p.l.c. analysis.
  
  
  RESULTS
  A high degree of variation in DPD activity was observed within each population (range CV = 34-48%). Median DPD activity also varied between these populations. South-west Asian and Kenyan subjects exhibited almost identical median values (192 and 193.5 pmol min(-1) mg(-1), respectively), which were similar to Caucasians (median 215 pmol min(-1) mg(-1). A significantly lower median DPD activity (119 pmol min(-1) mg(-1)) was observed in the Ghanaian population.
  
  
  CONCLUSIONS
  The similarity in DPD activity between Caucasian, Kenyan and South-west Asian populations suggests that the incidence of 5FU-related toxicity may be comparable in these groups. The pharmacokinetic implications of lower activity amongst Ghanaians needs to be evaluated.
authors.affiliation: Department of Medicine & Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Morsman
authors.forename: J
authors.initials: J
authors.lastname: Sludden
authors.forename: M M
authors.initials: MM
authors.lastname: Ameyaw
authors.forename: J
authors.initials: J
authors.lastname: Githang'A
authors.forename: A
authors.initials: A
authors.lastname: Indalo
authors.forename: D
authors.initials: D
authors.lastname: Ofori-Adjei
authors.forename: H L
authors.initials: HL
authors.lastname: McLeod
mesh_terms: D000328:Adult; D000963:Antimetabolites / Q000009:adverse effects / Q000493:pharmacokinetics; D001208:Asia; D044466:Asian People; D044383:Black People; D002851:Chromatography, High Pressure Liquid; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics; D005869:Ghana; D006801:Humans; D007630:Kenya; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D044465:White People
chemical_list: D000963:Antimetabolites; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil