Present status and perspective of pharmacogenetics in Mexico

Abstract

Drug costs account for up to 24% of the country's health expenditure and there are 13,000 registered drugs being prescribed. Diabetes is the main cause of death in the country, with over 85% of diabetic patients currently under drug treatment. The importance of knowing interindividual variability in drug metabolism on Mexican populations is thus evident. The purpose of this article is to provide an overlook of the current situation of pharmacogenetic research in Mexico, focusing on drug-metabolizing enzymes, and the possibility of developing a phenotyping cocktail for Mexican populations. So far, 21 pharmacogenetic studies on Mexican population samples (Mestizos and Amerindian) have been published. These have reported interindividual variability through phenotyping and/or genotyping cytochromes: CYP2D6, 2C19, 2C9, 2E1, and phase II enzymes UGT and NAT2. Some cytochromes with important clinical implications have not yet been phenotyped in Mexican populations. The development of a cocktail adapted to them could be a significant contribution to a larger knowledge on drug response variability at a lower price and shorter time. There are validated phenotyping cocktails that present several practical advantages, being valuable, safe, and inexpensive tools in drug metabolism characterization, which require only a single experiment to provide information on several cytochrome activities.

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

“…Mexico is home to 68 genetically different ethnic groups which suggests urgency for an adequate collection, classification, and characterization of variants on genes that affect drug efficacy and safety. Published studies collect the identification and determination of allele frequencies of at least all PGKB level 1 variants in Mestizos (Cuautle-Rodriguez et al, 2014; Fricke-Galindo et al, 2014; Fricke-Galindo et al, 2016; Gonzalez-Covarrubias et al, 2017). Fewer studies have included Natives, NGs techniques, or genotype-phenotype assessments.…”

Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

“…A recent review by Cuautle-Rodriguez et al highlights the minute number of studies and genes associated with drug response that have been investigated in Mexican populations (Cuautle-Rodriguez et al, 2013). Current knowledge on genes and genotypes that affect drug safety and efficacy have been mostly reported on Caucasian populations hence, the use of validated variants to tailor drug use cannot be freely extrapolated to other countries (Daar and Singer, 2005;Flockhart et al, 2009).…”

Pharmacogenomic Assessment of Mexican and Peruvian populations

“…Indeed, the majority of Central and South America are largely uncharacterized in the pharmacogenomics literature [24]. Previous studies have shown that Mexican–Americans have lower frequencies of the CYP2D6*4 alleles than European populations, but similar CYP2E1 and CYP3A4 enzyme activity [24–26].…”

“…Indeed, the majority of Central and South America are largely uncharacterized in the pharmacogenomics literature [24]. Previous studies have shown that Mexican–Americans have lower frequencies of the CYP2D6*4 alleles than European populations, but similar CYP2E1 and CYP3A4 enzyme activity [24–26]. Significant differences between Mexican–American and Spanish populations have also been observed for the CYP2C9*2 polymorphism, with the Spanish population carrying at least double the amount of CYP2C9*2 alleles (16% vs 8% for Mexican–Americans, 7% for Mexican-Mestizos and 1% for Mexican-Tepehuanos) [27].…”