Roco, A.Nieto, E.Suárez, M.Rojo, M.Bertoglia, M.P.Verón, G.Tamayo, F.Arredondo, A.Cruz, D.Muñoz, J.Bravo, GSalas, P.Mejías, F.Godoy, G.Véliz, P.Quiñones, L.A.2021-11-262021-11-262020-04Frontiers in Pharmacology Volume 116 April 2020 Article number 3251663-9812http://repositorio.unab.cl/xmlui/handle/ria/21097Indexación. ScopusBackground: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables. Objective: The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients Methodology: DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0–3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910). Results: The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability. Conclusion: We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR. © Copyright © 2020 Roco, Nieto, Suárez, Rojo, Bertoglia, Verón, Tamayo, Arredondo, Cruz, Muñoz, Bravo, Salas, Mejías, Godoy, Véliz and Quiñones.enPharmacogenomicsAcenocoumarolAnticoagulationPharmacogeneticsArtículoAtribución 4.0 Internacional (CC BY 4.0)10.3389/fphar.2020.00325