Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects

摘要: Aims Dihydropyrimidine dehydrogenase (DPD) catalyses the reduction of pyrimidines, including anticancer agent 5-fluorouracil (5FU). Impaired 5FU degradation, through low DPD activity, has led to severe, life-threatening or fatal toxicity after administration 5FU. Complete deficiency is associated with inherited metabolic disease thymine uraciluria. Several mutations in gene encoding have recently been identified, but phenotype-genotype concordance these alterations general population not reported. Methods Mononuclear cells were isolated from whole blood and activity was determined ex vivo incubation 14C-5FU followed by h.p.l.c. analysis metabolites. Analysis at an exon splice site, codons 534, 543, 732, a deletion base 1897 (ΔC1897) performed 30 subjects lowest highest enzyme using PCR-RFLP. Results DPD measured 226 Caucasian highly variable (range 19.1–401.4 pmol min−1 mg−1 protein). Mutations frequently observed 543 (allele frequency 28%), 732 5.8%), 534 0.8%), activity. There no site ΔC1897 found this population. Conclusions The five analysed study are insufficient for identification patients risk Both mutation relatively rare population. Therefore, further molecular required facilitate use genetic diagnosis cancer therapeutics.