Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA Consortium Report on Population Pharmacogenomics.

Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their "predicted drug metabolism phenotypes" across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews.

CYP450 Genotype/Phenotype Concordance in Mexican Amerindian Indigenous Populations-Where to from Here for Global Precision Medicine?

Global precision medicine demands characterization of drug metabolism and phenotype variation in diverse populations, including the indigenous societies. A related question is the extent to which CYP450 drug metabolizing enzyme genotype and phenotype data are concordant and whether they can be used interchangeably. These issues are increasingly debated as precision medicine continues to expand as a popular research topic worldwide.

Lessons from Cuba for Global Precision Medicine: CYP2D6 Genotype Is Not a Robust Predictor of CYP2D6 Ultrarapid Metabolism.

A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping.

Pharmacogenetic research activity in Central America and the Caribbean: a systematic review.

Aim: The present review was aimed at analyzing the pharmacogenetic scientific activity in Central America and the Caribbean.

Materials & Methods: A literature search for pharmacogenetic studies in each country of the region was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers including 'phenotyping probe drugs' for major drug metabolizing enzymes. The review included 132 papers involving 47 biomarkers and 35,079 subjects (11,129 healthy volunteers and 23,950 patients).

Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population.

CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry.

Worldwide interethnic variability and geographical distribution of CYP2C9 genotypes and phenotypes.

Introduction: Notably differences in CYP2C9 allele frequencies among worldwide populations have been reported, with an interesting low frequency of the CYP2C9*2 allele in Amerindians compared with Admixed and European populations.

Areas Covered: Literature was searched using the PubMed database and was focused on worldwide original research papers on CYP2C9 alleles and CYP2C9 phenotypes ("predicted" from CYP2C9 genotypes and "measured" metabolic phenotype with a probe drug) among healthy volunteers according to their ethnicity and geographical distribution. Seventy-eight original research articles including a total of 31,978 subjects were identified.

Ethnic background and CYP2D6 genetic polymorphisms in Costa Ricans.

CYP2D6 differences have already been demonstrated within Latin American populations by the CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics (RIBEF, as per the acronym in Spanish). However, within the population of Costa Rica, no research has been conducted until now, even though this population has a trihybrid component ancestry that represents an interesting condition.

Pharmacogenetics in Central American healthy volunteers: interethnic variability.

Ethnicity is one of the major factors involved in interindividual variability to drug response. This study aims to describe the frequency of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in Central American healthy volunteers and to determine its interethnic variability. Twenty-six original research articles on allelic, genotypes or metabolic phenotype frequencies were analyzed, in which a total number of 7611 Central American healthy volunteers were included (6118 were analyzed for genotype and 1799 for metabolic phenotype).

Interethnic variability of CYP2D6 alleles and of predicted and measured metabolic phenotypes across world populations.

Introduction: The frequency of CYP2D6 alleles, related to either a lack of or increased enzymatic activity, which may lead to poor metabolism (PM) or ultrarapid metabolism (UM), can vary across ethnic groups and hence across geographic regions.

Areas Covered: Worldwide original research papers on CYP2D6 allelic frequencies, metabolic phenotype frequencies measured with a probe drug, and/or genotype frequencies that studied > 50 healthy volunteers, were included in analyses to describe the distributions of alleles, phenotypes predicted from genotypes (predicted poor metabolizers [gPMs], predicted ultrarapid metabolizers [gUMs]) and metabolic phenotypes (mPMs, mUMs) across ethnic groups and geographic regions. The analysis included 44,572 individuals studied in 172 original research papers.

CYP2D6 gene polymorphisms and predicted phenotypes in eight indigenous groups from northwestern Mexico.

Aim: Polymorphisms in CYP2D6 impact the interindividual and interethnic variability of drug efficiency; therefore, we determined the CYP2D6 allele distribution in eight Amerindian groups from northwestern Mexico and compared them with the frequencies in Mexican Mestizos.

Materials & Methods: A total of 508 Amerindians were studied. Genotyping of CYP2D6*5 and multiplication alleles was performed by long-range PCR, while CYP2D6*2, *3, *4, *6, *10, *17, *29, *35, *41 and copy number were evaluated by real-time PCR.

Characterization of CYP2D6 genotypes and metabolic profiles in the Portuguese population: pharmacogenetic implications.

Aim: CYP2D6 codes for a protein that is vastly involved in the metabolism of various substances. This gene is highly polymorphic, which influences the enzymatic activity and contributes to the huge variability in the enzyme hydroxylation capacity. Different metabolic profiles determine the processing of xenobiotics and endobiotics, thereby influencing disease risk, therapeutic efficacy and side effects, or toxicity of xenobiotics.

Evaluation of drug-metabolizing enzyme hydroxylation phenotypes in Hispanic populations: the CEIBA cocktail.

Interindividual differences in response to drug treatments are mainly caused by differences in drug metabolism, in which cytochrome P450 (CYP450) enzymes are involved. Genetic polymorphisms of these enzymes have a key role in this variability. However, environmental factors, endogenous metabolism and disease states also have a great influence on the actual drug metabolism rate (metabolic phenotype).

High-performance liquid chromatography method using ultraviolet detection for the quantification of aripiprazole and dehydroaripiprazole in psychiatric patients.

Background: Aripiprazole (ARI) is an antipsychotic drug that is metabolized to dehydroaripiprazole (DARI) by CYP2D6. Because of the large interindividual variability in ARI and DARI plasma concentrations, therapeutic drug monitoring may be of use in psychiatric patients during treatment with ARI. The aim of the present study was to develop a simple and reliable method for the quantitative determination of ARI and DARI in plasma using liquid-liquid extraction and reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection.