Fenotipos metabólicos de dextrometorfano y losartán, genotipos CYP2D6 y CPY2C9 en la poblacion ecuatoriana respecto de la española

Laburpena

The present doctoral thesis was aimed at describing 1) the relationship between the CYP2D6 and CYP2C9 genotypes and the dextromethorphan and losartan hydroxylation phenotypes in Ecuadorian mestizos, as well as 2) the differences in these variables bewteen this Ecuadorian population and a Spanish one. The participants were 318 unrelated healthy volunteers from Ecuador. Genotyping of CYP2D6 (CYP2D6 *2, *3, *4, *5, *6, *10, *17, *29, *35, *41, and copy number) and CYP2C9 (CYP2C9*2, *3, *4, *5, *6) as well as the plasma levels of dextromethorphan and its metabolite (dextrorphan), and urinary losartan and its carboxylic acid metabolite (E3174) were analyzed. Only 0.9% and were classified as poor metabolizers and 0% was ultrarapid. These and the frequencies of CYP2D6 alleles related to null (14%) or increased activity (0.8%) were lower than in Spaniards, with the exception of that of reduced function alleles (5.1%). Similarly, the frequencies of CYP2C9*2 (5.4%) and *3 (1.5%) were also lower than in the Spanish population, and the urinary losartan/E3174 ratio was higher in CYP2C9*1/*3 carriers than in subjects with the CYP2C9*1/*1 genotype. Present data show that interindividual variation in dextromethorphan and losartan hydroxylation phenotypes is influenced by CYP2D6 and CYP2C9 genetic polymorphisms in Ecuadorians. Furthermore, results also show interethnic variability in the metabolism of CYP2D6 and CYP2C9 substrates, given the differences found between Ecuadorians and Spaniards.