Exploring Variation in Known Pharmacogenetic Variants and its Association with Drug Response in Different Mexican Populations
Information on genetic variants that affect the pharmacokinetics and pharmacodynamics (PK/PD) of drugs in different populations from Mexico is still an ongoing endeavor. Here, we investigate allele frequencies on pharmacogenetic targets in Mexican Mestizos and Natives from three different States and its association with drug efficacy in individuals receiving either anticoagulants or antipsychotic drugs.
Natives from three different states and Mestizo patients receiving acenocoumarol or antipsychotics were genotyped using the DMET microarray (Affymetrix).
We provide a collection of genetic variants that indicate that there are 3-times more variation than similarities between populations from Mexico and major continental groups. These differences were observed in several relevant targets including ABCB1, SLCO1A1, NAT2, UGTs, TYMS, VKORC1, and NR1I3. Moreover, Mexican Mestizos also showed allele frequency differences when compared to Natives for variants on DPYD, ADH1A, CYP3A4, SLC28A3, and SLC28A1. Significant allele differences also arose among the three Native groups here studied, mostly for transporters of the ABC-binding cassette and the solute carrier gene family. Finally, we explored genotype-drug response associations and pinpointed variants on FMOs (coumarins), and GSTM1 (haloperidol).
These findings confirm previous results and further delve into the pharmacogenetics of Mexican populations including different Native groups.
KEY WORDSantipsychotics coumarins Mexican populations pharmacogenetics
Absorption, distribution, metabolism, and elimination
Adverse drug reactions
Glutathione S-Transferase Mu 1
International normalized ratio (INR) is a calculation based on prothrombin time
- 9.Fricke-Galindo I, Jung-Cook H, A LL, Lopez-Lopez M. Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics). Drug Metabol Personal Ther. 2016.Google Scholar
- 13.Jittikoon J, Mahasirimongkol S, Charoenyingwattana A, Chaikledkaew U, Tragulpiankit P, Mangmool S, et al. Comparison of genetic variation in drug ADME-related genes in Thais with Caucasian, African and Asian HapMap populations. J Hum Genet. 2015.Google Scholar
- 16.Aminkeng F, Ross CJD, Rassekh SR, Brunham LR, Sistonen J, Dube MP, et al. Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent. Pharmacogenomics J. 2014;14(2):160–70.CrossRefPubMedGoogle Scholar
- 18.Cuautle-Rodriguez P, Llerena A, Molina-Guarneros J. Present status and perspective of pharmacogenetics in Mexico. Drug Metabol Drug Interact. 2013. p. 37.Google Scholar
- 20.Jackson JN, Long KM, He Y, Motsinger-Reif AA, McLeod HL, Jack J. A comparison of DMET Plus microarray and genome-wide technologies by assessing population substructure. Pharmacogenet Genomics. 2016.Google Scholar
- 22.Kwara A, Lartey M, Boamah I, Rezk NL, Oliver-Commey J, Kenu E, et al. Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c Is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009;49(9):1079–90.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Ortega-Vazquez A, Dorado P, Fricke-Galindo I, Jung-Cook H, Monroy-Jaramillo N, Martinez-Juarez IE, et al. CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy. Pharmacogenomics J. 2015.Google Scholar