Jm. Morsman et al., Evaluation of dihydropyrimidine dehydrogenase activity in South-west Asian, Kenyan and Ghanaian populations, BR J CL PH, 50(3), 2000, pp. 269-272
Aims Dihydropyrimidine dehydrogenase (DPD) reduces endogenous pyrimidines a
nd 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 wa
s assessed in South-west Asian, Kenyan and Ghanaian populations.
Methods DPD activity was determined in peripheral mononuclear cells using [
C-14]-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 th
ese populations. South-west Asian and Kenyan subjects exhibited almost iden
tical median Values (192 and 193.5 pmol min(-1) mg(-1), respectively), whic
h were similar to Caucasians (median 215 pmol min(-1) mg(-1)). A significan
tly 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 So
uthwest Asian populations suggests that the incidence of 5FU-related toxici
ty may be comparable in these groups. The pharmacokinetic implications of l
ower activity amongst Ghanaians needs to be evaluated.