Pharmacogenetic Study of the Dihidropyrimidine Dehidrogenase Gene (DPYD)
The DPYD PGx test is a pharmacogenetic test focused on fluoropyrimidine drugs:
The dihydropyrimidine dehydrogenase enzyme metabolises the endogenous pyrimidines thymine and uracil and is also critical to the metabolism of fluoropyrimidine drugs. This enzime is responsible for the inactivation of approximately 80-85% of 5-fluorouracil. According to the EMA (assessment report EMA/274404/2020) the frequency of partial and complete dihydropyrimidine dehydrogenase deficiency among Caucasians is approximately 3%–9% and 0.01%–0.5%, respectively. Using fluoropyrimidines to treat patients with these deficiencies can result in severe toxicity.
For this reason, testing for dihydropyrimidine dehydrogenase deficiency before treatment with these fluoropyrimidines is recommended by the Infarmed (the Portuguese national authority of medicines and health products) and the European Medicines Agency (EMA).
This pharmacogenetic test analysis the following nine alleles of the DPYD gene:
HapB3, *2A, *6, *7, *8, *10, *12, *13, c.2846A>T
The interrogation of alleles associated with reduced activity of the enzyme dihydropyrimidine dehydrogenase allows identifying the individuals with reduced metabolizer capacity who, therefore, benefit from lower fluoropyrimidine doses and closer monitoring of side effects.
The Clinical Pharmacogenetics Implementation Consortium (CPIC®) and the Dutch Pharmacogenetics Working Group (DPWG) are professional societies that provide practice pharmacogenetic guidelines. Both groups have published recommendations for fluoropyrimidine drug therapy based on DPYD genotyping data, aiming to minimise adverse drug toxicity and thus provide greater safety to patients.
The pharmacogenetic testing report includes the calculation of the activity score for the dihydropyrimidine dehydrogenase enzyme, based on the obtained genotype, and its translation into practical recommendations according to the most recent guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC®) and the Dutch Pharmacogenetics Working Group (DPWG). The way this information is provided allows an instant understanding of the implications of the obtained results.
The associations identified between the genetic variants and the micronutrient needs and sensitivities reported in MyWellnessGenes® are corroborated by reliable international scientific studies [1, 2], including meta-analyses comprising very large cohorts [3-7]. Only peer reviewed scientific publications presenting statistically significant genotype-phenotype correlations have been considered.
 Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines.
 European Medicines Agency. 2020. EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine. EMA/229267/2020
 Infarmed. 2020. Circular Informativa: Fluorouracilo, capecitabina, tegafur e flucitosina – novas recomendações de segurança. N.º 072/CD/550.20.001 (18/03/2020)