Genomic Ancestry,CYP2D6,CYP2C9, andCYP2C19Among Latin Americans

Abstract

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. The study of a broad spectrum of Native American populations from different ethno-linguistic groups show how autochthonous diversity shaped the distribution of pharmaco-alleles and give insights on the prevalence of clinically relevant phenotypes associated with drugs, such as paroxetine, tamoxifen, warfarin, and clopidogrel.

A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy

“…Allele frequencies of CYP2C19 *1 were up to 1.4 times higher than those assessed in other populations (Caucasian, Asian, African, and Latin American) ( p < 0.05). Interestingly, CYP2C19*17 has a lower allele frequency (2.1 times) concerning populations of other ethnic origins, including Latin America [ 2 , 25 ]. The main LOF CYP2C19 *2 allele, previously related to interindividual variability of response to clopidogrel behaves similarly between Latin American populations but presents significant differences with Asian and European populations, in which this allele reaches values of 28% [ 26 ].…”

“…These results suggest that the Colombian population presents a pharmacogenetic profile of less susceptibility to low and high platelet reactivity in patients treated with the antiplatelet clopidogrel compared to other Latin American or world populations. Recently the RIBEF (Consortium of the Ibero-American Network of Pharmacogenetics and Pharmacogenomics) analyzed the frequency of CYP2C19 variants in several Latin American countries, nevertheless, Colombia was not included [ 25 , 27 ]. The results of this study contribute to fill this knowledge gap in the Latin American populations underlining high degree of genetic admixture.…”

Genetic admixture in Brazil

“…In general, autosomal biparental Native American ancestry in Brazil is low, compared with Mexico, Guatemala, Peru and Bolivia, the countries with the highest Native American ancestry in Latin America (Avena et al, 2012;Galanter et al, 2012;Leite, Fonseca, de França, Parra, & Pereira, 2011;Rodrigues-Soares et al, 2020;Ruiz-Linares, 2014;Salzano & Bortolini, 2002;Sandoval et al, 2013).…”

Pharmacogenetics in Psychiatry: Perceived Value and Opinions in a Chilean Sample of Practitioners

“…Another important issue is that, although CPIC and FDA guidelines are available for specific drug pairs, knowledge of their application and results in terms of health outcomes in Latin-American populations is practically nonexistent. In addition, there are differences in allelic composition and frequencies in several relevant genes, compared to European and other populations (Naranjo et al, 2018;Rodrigues-Soares et al, 2020), which may have an impact on clinical use in the region.…”