Brazilian Cohort and Genes Encoding for Drug-Metabolizing Enzymes and Drug Transporters

Abstract

Background & aim: Genetic variability in drug absorption, distribution, metabolism and excretion (ADME) genes contributes to the high heterogeneity of drug responses. The present study investigated polymorphisms of ADME genes frequencies and compared the findings with populations from other continents, available in the 1000 Genome Project (1 KGP) and the Exome Aggregation Consortium (ExAC) databases. Methodology & results: We conducted a study of 100 patients in Brazil and a total of 2003 SNPs were evaluated by targeted next-generation sequencing in 148 genes, including Phase I enzymes (n = 50), Phase II enzymes (n = 38) and drug transporters (n = 60). Overall, the distribution of minor allele frequency (MAF) suggests that the distribution of 2003 SNPs is similar between Brazilian cohort, 1 KGP and ExAC; however, we found moderate SNP allele-frequency divergence between Brazilian cohort and both 1000 KGP and ExAC. These differences were observed in several relevant genes including CYP3A4, NAT2 and SLCO1B1. Conclusion: We concluded that the Brazilian population needs clinical assessment of drug treatment based on individual genotype rather than ethnicity.

Comparison of dose-dense vs. 3-weekly paclitaxel and carboplatin in the first-line treatment of ovarian cancer in a propensity score-matched cohort

“…There are few data about distribution of pharmacogenetics polymorphisms among Brazilians, besides the fact that the Brazilian population is highly heterogeneous and admixed, which may cause high heterogeneity of drug responses [ 29 ]. A small study showed that the frequency of CYP2C8*2, for example, is similar to other registries, being more common in Brazilian black population (13% of the sample) and rare for white and Asian Brazilians (1 and 0%, respectively) [ 30 ]. The exact role and clinical impact of the pharmacogenetic ethnic variations have yet to be clarified, and an improved understanding about this topic may eventually help to explain the conflicting results between the studies.…”

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

“…The contribution of the genetic component on the pattern or susceptibility to diseases in the Brazilian population has already been shown to have an impact on the control and treatment of infectious, autoimmune, and hematological diseases, drug pharmacokinetics, and even on the transplant allocation system [ 13 , 14 , 19 , 55 , 56 ].…”

“…From a public health system perspective, epidemiological features of cardiovascular health in developing countries have been described [ 16 , 17 ], but there is still an urgent need for studies with geographic representation to allow both regional and ethnic diversity as essential elements to data acquisition and analysis of CVD risk. We designed the case-control study CardioVascular-Genes (CV-GENES) to determine the population attributable fraction estimates of genetic profile in the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events, after adjustment for potentially modifiable CVD risk factors in Brazil [ 18 , 19 ].…”

Impact of Genetic Background as a Risk Factor for Atherosclerotic Cardiovascular Disease: A Protocol for a Nationwide Genetic Case-Control (CV-GENES) study in Brazil

“…The contribution of the genetic component on the pattern or susceptibility to diseases in the Brazilian population has already been shown to have an impact on the control and treatment of infectious, autoimmune, and hematological diseases, drug pharmacokinetics, and even on the transplant allocation system. [13,14,19,48,49] Knowing the true impact on the Brazilian population may prompt the implementation of population genetic screening programs for strict control of cardiovascular risk factors and/or indicate changes in therapeutic targets and clinical control.…”

“…To reliably answer this question, a genetic case-control study (CV-GENES) was designed to evaluate the contribution of genetic background adjusted for traditional modifiable cardiovascular risk factors, in a nationwide Brazilian cohort. [18,19] The primary aim of the current study is to assess the association of genomics to ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events on a population level.…”