Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration

Author(s)

Junior Lima Santos, Paulo Caleb ^[1] ; Marcatto, Leiliane Rodrigues ^[1] ; Duarte, Nubia Esteban ^[1] ; Gadi Soares, Renata Alonso ^[1] ; Cassaro Strunz, Celia Maria ^[2] ; Scanavacca, Maurcio ^[3] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre Costa ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, Clin Lab, BR-05403000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Heart Inst InCor, Clin Cardiol Div, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: PHARMACOGENOMICS; v. 16, n. 8, p. 865-876, 2015.
• Web of Science Citations: 14

Abstract

Background: The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population. Materials \& methods: We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133). Results: Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms. Conclusion: Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available. (AU)

• FAPESP's process: 13/20614-3 - Pharmacogenetic analyses for cardiovascular drugs focusing on implementation
• Grantee: Paulo Caleb Júnior de Lima Santos
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/09295-3 - Pharmacogenetic of cardiovascular system drugs focusing on implementation
• Grantee: Paulo Caleb Júnior de Lima Santos
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/00316-5 - Mixed Models in Genetic mapping using Family-Based Designs and platforms of SNPs
• Grantee: Nubia Esteban Duarte
• Support Opportunities: Scholarships in Brazil - Post-Doctoral