Evaluation of dihydropyrimidine dehydrogenase activity in South‐west Asian, Kenyan and Ghanaian populations

Aims 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.

DOI: 10.1046/j.1365-2125.2000.00242.x

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