genotype-phenotype correlation: current insights and unanswered questions.

The CYP2C19 enzyme is implicated in the metabolism of several clinically used drugs. Its phenotype is usually predicted by genotyping and indicates the expected enzymatic activity for each patient. However, with a few exceptions, genotyping has not resulted in a reliable prediction of the metabolizer status, since most of the evidence currently available for this prediction comes from research into populations of predominantly European ancestry.

Pharmacogenetics: ethnicity, treatment and health in Latin American populations.

The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) studies Latin American populations to benefit from the implementation of personalized medicine. Since 2006, it has studied ethnicity to apply pharmacogenetics knowledge in autochthonous populations of Latin America, considering ancestral medicine. The meeting 'Pharmacogenetics: ethnicity, Treatment and Health in Latin American Populations' was held in Mexico City, Mexico, and presented the relevance of RIBEF collaboration with Latin American researchers and the governments of Mexico, Spain and the Autonomous Community of Extremadura.

Relationships between CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 metabolic phenotypes and genotypes in a Nicaraguan Mestizo population.

Interethnic variability in the drug-metabolizing capacity of CYP450 enzymes may lead to discrepancies in the relationship between genotypes and phenotypes worldwide. The present study was aimed to analyze for the first time whether there is a relationship between clinically relevant CYP450 genetic polymorphisms and their drug oxidation capacity (metabolic phenotype) in a population of healthy Nicaraguan volunteers. Two hundred and twelve participants were genotyped for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, and their actual metabolic phenotype (evaluated by the Metabolic Ratio, MR) was analyzed by using the CEIBA cocktail approach.

Challenges and Opportunities for Clinical Pharmacogenetic Research Studies in Resource-limited Settings: Conclusions From the Council for International Organizations of Medical Sciences-Ibero-American Network of Pharmacogenetics and Pharmacogenomics Meeting.

Purpose: The symposium Health and Medicines in Indigenous Populations of America was organized by the Council for International Organizations of Medical Sciences (CIOMS) Working Group on Clinical Research in Resource-Limited Settings (RLSs) and the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF). It was aimed to share and evaluate investigators' experiences on challenges and opportunities on clinical research and pharmacogenetics.

Methods: A total of 33 members from 22 countries participated in 2 sessions: RIBEF studies on population pharmacogenetics about the relationship between ancestry with relevant drug-related genetic polymorphisms and the relationship between genotype and phenotype in Native Americans (session 1) and case examples of clinical studies in RLSs from Asia (cancer), America (diabetes and women health), and Africa (malaria) in which the participants were asked to answer in free text their experiences on challenges and opportunities to solve the problems (session 2).

Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans.

We present the distribution of CYP2D6, CYP2C9, and CYP2C19 variants and predicted phenotypes in 33 native and admixed populations from Ibero-America (n > 6,000) in the context of genetic ancestry (n = 3,387). Continental ancestries are the major determinants of frequencies of the increased-activity allele CYP2C19*17 and CYP2C19 gUMs (negatively associated with Native American ancestry), decreased-activity alleles CYP2D6*41 and CYP2C9*2 (positively associated with European ancestry), and decreased-activity alleles CYP2D6*17 and CYP2D6*29 (positively associated with African ancestry). For the rare alleles, CYP2C9*2 and CYPC19*17, European admixture accounts for their presence in Native American populations, but rare alleles CYP2D6*5 (null-activity), CYP2D6-multiplication alleles (increased activity), and CYP2C9*3 (decreased-activity) were present in the pre-Columbian Americas.

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.