The Influence of Ethnicity on Warfarin Dosage Requirements in the Chilean Population

Abstract

Background: Vitamin K antagonists are drugs that are widely prescribed around the world and their use has helped improve the prognosis of patients with thromboembolic disease. However, a high interindividual variability has been observed in dosage requirements to reach the desired anticoagulation range that could be due to environmental and genetic factors. Studies suggest that ethnicity influences coumarin response, supporting the observed differences in dose requirements across various populations. Studies using mitochondrial DNA (mtDNA) markers have suggested that the Chilean population has a predominantly Amerindian genetic pool. Objective: To evaluate the influence of ethnicity, defined by the presence of Amerindian mtDNA haplogroups, on the variability in therapeutic response to warfarin in the Chilean population. Methods: A total of 191 patients treated with warfarin were included in this study. Analysis of the mitochondrial genome for detecting the presence of Amerindian mtDNA haplogroups was performed using polymerase chain reaction and polymerase chain reaction restriction fragment length polymorphism techniques. The evaluation of warfarin requirements according to each haplogroup was performed by ANOVA with a 95% CI and assuming statistical significance at P < 0.05. Results: Based on the presence of an mtDNA haplogroup, 91% of the Chilean population had an Amerindian background. There were no significant differences in warfarin dosage requirements among the different Amerindian haplogroups (P = 0.083). Conclusions: The presence of Amerindian mtDNA haplogroup does not influence warfarin dosage requirements in the Chilean population.

Keywords

• anticoagulant therapy
• mitochondrial DNA
• pharmacogenomics
• warfarin