Pharmaceutical Research

, Volume 33, Issue 11, pp 2644–2652 | Cite as

Exploring Variation in Known Pharmacogenetic Variants and its Association with Drug Response in Different Mexican Populations

  • Vanessa Gonzalez-Covarrubias
  • José Jaime Martínez-Magaña
  • Regina Coronado-Sosa
  • Beatriz Villegas-Torres
  • Alma D. Genis-Mendoza
  • Pablo Canales-Herrerias
  • Humberto Nicolini
  • Xavier Soberón
Research Paper

Abstract

Purpose

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.

Methods

Natives from three different states and Mestizo patients receiving acenocoumarol or antipsychotics were genotyped using the DMET microarray (Affymetrix).

Results

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).

Conclusions

These findings confirm previous results and further delve into the pharmacogenetics of Mexican populations including different Native groups.

KEY WORDS

antipsychotics coumarins Mexican populations pharmacogenetics 

ABBREVIATIONS

ADME

Absorption, distribution, metabolism, and elimination

ADRs

Adverse drug reactions

FMO

Flavin monooxygenase

GSTM1

Glutathione S-Transferase Mu 1

INR

International normalized ratio (INR) is a calculation based on prothrombin time

PD

Pharmacodynamics

PK

Pharmacokinetics

Supplementary material

11095_2016_1990_MOESM1_ESM.xlsx (236 kb)
ESM 1(XLSX 236 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Vanessa Gonzalez-Covarrubias
    • 1
  • José Jaime Martínez-Magaña
    • 2
  • Regina Coronado-Sosa
    • 1
  • Beatriz Villegas-Torres
    • 3
  • Alma D. Genis-Mendoza
    • 2
    • 4
  • Pablo Canales-Herrerias
    • 1
  • Humberto Nicolini
    • 2
    • 4
  • Xavier Soberón
    • 1
  1. 1.Laboratorio de FarmacogenómicaInstituto Nacional de Medicina Genómica (INMEGEN)Ciudad de MexicoMexico
  2. 2.Laboratorio de Genomica de Enfermedades Psiquiatricas y NeurodegenerativasInstituto Nacional de Medicina Genomica (INMEGEN)Ciudad de MexicoMexico
  3. 3.Laboratorio de Diagnostico GenomicoInstituto Nacional de Medicina Genómica (INMEGEN)Ciudad de MexicoMexico
  4. 4.Servicios de Atención Psiquiatrica (SAP) Secretaria de SaludCiudad de MexicoMexico

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