Evolution of dihydropyrimidine dehydrogenase diagnostics in a single center in a time-period of eight years

Publication date: Available online 31 October 2018Source: Current Therapeutic ResearchAuthor(s): Marieke J.H. Coenen, Aimée D.C. Paulussen, Marc Breuer, Martijn Lindhout, Demis C.J. Tserpelis, Anja Steyls, Jörgen Bierau, Bianca J.C. van den BoschAbstractPurposeFluoropyrimidine treatment can be optimized based on DPD (dihydropyrimidine dehydrogenase) activity. DPD dysfunction leads to an increased exposure to active metabolites, which can result in severe or even fatal toxicity.MethodsWe provide an overview of eight years DPD diagnostics (n=1194).ResultsWithin the study period our diagnostic test has evolved from a single enzyme measurement using first a radiochemical and then a non-radiochemical assay by Ultra-High Performance Liquid chromatography – Mass Spectrometry (UHPLC-MS) in peripheral blood mononuclear cells (PBMCs) with uracil, to a combined enzymatic and genetic test (PCR (Polymerase Chain Reaction) followed by Sanger sequence analysis) of four variants in the DPYD gene (DPYD*2A, DPYD*13, c.2846A>T and 1129-5923C>G; allele frequencies respectively 0.58%, 0.03%, 0.29% and 1.35%). Patients who have one of the four variants tested (n=814) have a lower enzyme activity than the overall patient group. The majority of patients with the DPYD*2A variant (83%) consistently showed a decreased enzyme activity. Only 24 (25.3%) of the 95 patients with a low enzyme activity (tested for four variants) carried a variant. Complete DPYD sequencing in a subgroup with low enzyme act...
Source: Current Therapeutic Research - Category: Drugs & Pharmacology Source Type: research