AUTHOR=Gonzalez-Covarrubias Vanessa , Urena-Carrion Javier , Villegas-Torres Beatriz , Cossío-Aranda J. Eduardo , Trevethan-Cravioto Sergio , Izaguirre-Avila Raul , Fiscal-López O. Javier , Soberon Xavier 

TITLE=Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00863

DOI=10.3389/fphar.2017.00863

ISSN=1663-9812

ABSTRACT=<p>Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on <italic>CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS</italic>, and <italic>GGCX, VKORC1, CYP2C18, NQO1</italic>. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, <italic>CYP1A1, CYP3A4, CYP3A5</italic>, and <italic>F8</italic>, and a low proportion of novel-to-known variants on <italic>CYP2E1, VKORC1</italic>, and <italic>SULT1A1/2</italic>. Using a Bayesian approach, we identified variants influencing acenocumarol dosing on, <italic>VKORC1 (2), SULT1A1 (1)</italic>, and <italic>CYP2D8P (1)</italic> explaining 40–55% of dose variability. A collection of pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also presented. Our results offer an initial insight into the use of a targeted NGS approach in the pharmacogenomics of coumarins in Mexican Mestizos.</p>