Impact assessment of the inclusion of ABCB1 and CYP4F2 genes polymorphisms in pharmacogenetic-guided algorithm for personalized warfarin dosing

• Grant number: 16/22507-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2017
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Paulo Caleb Júnior de Lima Santos
• Grantee: Letícia Camargo Tavares
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/09295-3 - Pharmacogenetic of cardiovascular system drugs focusing on implementation, AP.JP

Abstract

Cardiovascular diseases are one of the main causes of mortality worldwide. Among them, there are the thromboembolic disorders. The warfarin, drug classified as coumarin oral anticoagulant, is widely used to treat these clinical conditions. However, according to genetic and environmental factors, coumarins have shown high variance in pharmacokinetic and pharmacodynamics, resulting in distinct pharmaceutical interindividual responses. Therefore, with great potential of applicability and efficacy in clinical treatments, pharmacogenetics algorithms have been developed to set personalized therapeutics. Thereby, the aim of this research project is to assess the impact of the inclusion of ABCB1 and CYP4F2 gene polymorphisms, which indicate warfarin resistance, as variables of the pharmacogenetics algorithm for personalized warfarin dosing previously developed by the Genetics and Molecular Cardiology Group, Heart Institute (InCor) (R² = 40%) (Santos PC et al, 2015). It is expected that the inclusion of these variables can improve the accuracy of this pharmacogenetics algorithm. For this study, 965 patients, enrolled in the Clinical Arrythmia and Pacemaker Units Heart Institute (InCor), University of São Paulo Medical School (HC/USP), will be involved. The genotypic analysis of ABCB1 c.3435C>T and CYP4F2 c.1297G>A will be performed by genomic DNA amplification by polymerase chain reaction (PCR), followed by melting curve analysis (HRM-PCR) and TaqMan® assay. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

EL ROUBY, NIHAL; RODRIGUES MARCATTO, LEILIANE; CLAUDIO, KARLA; CAMARGO TAVARES, LETICIA; STEINER, HEIDI; BOTTON, MARIANNA R.; LUBITZ, STEVE A.; FALLON, ECHO N.; YEE, KEVIN; KAYE, JUSTIN; et al. Multi-site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos. CTS-CLINICAL AND TRANSLATIONAL SCIENCE, v. 14, n. 1, SEP 2020. (16/22507-8, 13/09295-3)

TAVARES, LETICIA C.; MARCATTO, LEILIANE R.; SANTOS, PAULO C. J. L.. Genotype-guided warfarin therapy: current status. PHARMACOGENOMICS, v. 19, n. 7, p. 667-685, MAY 2018. (16/23454-5, 13/09295-3, 16/22507-8)

TAVARES, LETICIA C.; MARCATTO, LEILIANE R.; SOARES, RENATA A. G.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C.; SANTOS, PAULO C. J. L.. Association Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patients. FRONTIERS IN PHARMACOLOGY, v. 9, MAY 23 2018. (16/23454-5, 13/09295-3, 16/22507-8)

TAVARES, LETICIA C.; DUARTE, NUBIA E.; MARCATTO, LEILIANE R.; SOARES, RENATA A. G.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C.; JUNIOR LIMA SANTOS, PAULO CALEB. Impact of incorporating ABCB1 and CYP4F2 polymorphisms in a pharmacogenetics-guided warfarin dosing algorithm for the Brazilian population. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, v. 74, n. 12, p. 1555-1566, DEC 2018. (16/22507-8, 16/23454-5, 13/09295-3)

MARCATTO, LEILIANE RODRIGUES; SACILOTTO, LUCIANA; TAVARES, LETICIA CAMARGO; PEREIRA SOUZA, DEBORA STEPHANIE; OLIVETTI, NATALIA; CASSARO STRUNZ, CELIA MARIA; COSTA DARRIEUX, FRANCISCO CARLOS; SCANAVACCA, MAURICIO IBRAHIM; KRIEGER, JOSE EDUARDO; PEREIRA, ALEXANDRE COSTA; et al. Evaluation of the Long-Term Impact on Quality After the End of Pharmacist-Driven Warfarin Therapy Management in Patients With Poor Quality of Anticoagulation Therapy. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 14 2020. (16/23454-5, 16/22507-8, 13/09295-3, 19/08338-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

TAVARES, Letícia Camargo. Impact evaluation of incorporating ABCB1 and CYP4F2 polymorphisms in a genetic-guided warfarin dosing algorithm. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.