Page 16 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg
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Chapter 1
the compound heterozygous patients.50 These patients carry multiple DPYD variants and the effect of the DPYD variants on the DPD enzyme activity cannot be predicted using the gene activity score. We determine the prevalence of these patients using several publicly available databases. In addition, we describe a few patient cases and apply additional genotyping assays to determine the location of the DPYD variants on the alleles (phasing), in order to determine a gene activity score and predict the DPD phenotype. In chapter 12 we describe a genome-wide association study. It is expected that other enzymes besides DPD, and thus other genes besides DPYD, are involved in the onset of severe fluoropyrimidine-induced toxicity. With the genome-wide approach we aim to discover other variants, outside the DPYD gene, which are associated to the onset of severe fluoropyrimidine-induced toxicity.
This thesis ends with a general discussion, including future perspectives (chapter 13), followed by an English and Dutch summary (chapter 14).
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