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Pharm Res. 2016 Nov;33(11):2644-52. doi: 10.1007/s11095-016-1990-5. Epub 2016 Jul 7.

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

Author information

1
Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de Mexico, Mexico. vgonzalez@inmegen.gob.mx.
2
Laboratorio de Genomica de Enfermedades Psiquiatricas y Neurodegenerativas, Instituto Nacional de Medicina Genomica (INMEGEN), Ciudad de Mexico, Mexico.
3
Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de Mexico, Mexico.
4
Laboratorio de Diagnostico Genomico, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de Mexico, Mexico.
5
Servicios de Atención Psiquiatrica (SAP) Secretaria de Salud, Ciudad de Mexico, Mexico.

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.

KEYWORDS:

Mexican populations; antipsychotics; coumarins; pharmacogenetics

PMID:
27387170
DOI:
10.1007/s11095-016-1990-5
[Indexed for MEDLINE]

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