Analysis of the dihydropyrimidine dehydrogenase polymorphism in a British population

Subjects with low or absent dihydropyrimidine dehydrogenase activity (DPD) are at risk of excessive toxicity or death when undergoing fluoropyrimidine chemotherapy. The DPD polymorphism has not been well characterized in the general population and the frequency of the enzyme deficiency is not known. In preparation for a population multicentre analysis of DPD activity, a comparison of sample preparation methods and a pilot study in normal volunteer subjects was performed. The stability of peripheral blood mononuclear cell DPD activity at -70 degrees C was determined in 35 mM sodium phosphate buffer with 10% glycerol, 100% fetal calf serum (FCS) or as a dry pellet. DPD activity declined in FCS and increased in glycerol buffer, both reaching a plateau value 14 days after blood sampling. The glycerol buffer method was then used to study DPD activity in 50 British subjects (36 M: 14F; 20-56 years). A 8.4-fold range in DPD activity was observed (30.4-256 pmol min-1 mg-1 protein). DPD activity was not influenced by age or cigarette smoking. This information will facilitate analysis of the DPD polymorphism in populations from different countries and ethnic groups.