Evaluation of dihydropyrimidine dehydrogenase activity in South-west Asian, Kenyan and Ghanaian populations.
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.
Morsman
J M
JM
Department of Medicine & Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Sludden
J
J
Ameyaw
M M
MM
Githang'A
J
J
Indalo
A
A
Ofori-Adjei
D
D
McLeod
H L
HL
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
D000963:Antimetabolites; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil