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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  CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS , and  GGCX, VKORC1, CYP2C18, NQO1 . 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,  CYP1A1, CYP3A4, CYP3A5 , and  F8 , and a low proportion of novel-to-known variants on  CYP2E1, VKORC1 , and  SULT1A1/2 . Using a Bayesian approach, we identified variants influencing acenocumarol dosing on,  VKORC1 (2), SULT1A1 (1) , and  CYP2D8P (1)  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.

Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol