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.

Proteomics study of the effect of high-fat diet on rat liver

“…As the most important detoxification organ, the liver contains most of the phase I and phase II metabolic enzymes, which affect the metabolism of endogenous and exogenous substances (29) . KEGG pathway analysis revealed that metabolism of xenobiotics Fig.…”