title: Pharmacogenetics of drug metabolizing enzymes in Brazilian populations.
abstract: Phase I and II drug metabolizing enzymes (DMEs) play an important role in biotransformation of endogenous and exogenous compounds including drugs currently used in pharmacoterapy. Moreover, the genetic variability of DMEs causes important interindividual differences in drug and metabolite exposure, drug response, and risk of adverse drug reactions. We reviewed pharmacogenetics/pharmacogenomics (PGx) studies that evaluated the influence of polymorphisms in the CYPs genes - mainly CYP1, CYP2 and CYP3 gene families - and in the phase II genes - TPMT, NAT2, GSTs and UGTs - on therapeutic response in Brazilian cohorts. Ethnic admixture of Brazilians resulted in a population characterized by a unique genetic profile, in which ancestry informative markers change continuously among ethnic groups. Therefore, some of the PGx biomarkers have a different distribution among Brazilians and PGx data from well-defined ethnic groups are not applicable to Brazilian populations. PGx data focused on phase I and phase II DMEs from Brazilian studies are needed in order to establish the influence of the genetic diversity on therapeutic response to clinically relevant drugs in a population with a composition from a complex genetic admixture. These studies and their impact are discussed in this review.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cerda
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D001711:Biotransformation / Q000235:genetics; D001938:Brazil / Q000208:ethnology; D003580:Cytochromes / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008780:Methyltransferases / Q000235:genetics; D010597:Pharmacogenetics / Q000706:statistics & numerical data*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014166:Transferases / Q000235:genetics*; D000099148:UGT1A1 Enzyme
chemical_list: D001191:Arylamine N-Acetyltransferase; D003580:Cytochromes; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D008780:Methyltransferases; D014166:Transferases; D000099148:UGT1A1 Enzyme; C022745:thiopurine methyltransferase; C478900:NAT2 protein, human