Relationship Between EPHX1 Gene Polymorphism and Warfarin Resistance

Abstract

Introduction: Warfarin is an oral anticoagulant with a major role in thrombosis prevention. In clinical practice, the warfarin anticoagulant effect should be regularly observed using the international normalized ratio (INRs) to ensure a proper, safe, and effective dose. Many factors can affect the variability of warfarin dose. Several studies confirmed the possible clinical use of genotype-guided warfarin starting dose to provide a safe anticoagulation therapy. Aim: This cross-sectional study aimed to identify the potential importance of EPHX1 gene polymorphism (rs2292566) in warfarin resistance. Patients and Methods: Thirty patients with warfarin resistance (>10 mg/ day) not reaching targeted INR (2-3) (Group 1) were enrolled in this study besides 10 patients with optimum response warfarin (Group 2). All patients were subjected to history taking, clinical examination, and laboratory investigation of EPHX1 gene polymorphism by PCR. Results: 27 patients (90%) of group1 were of GG genotype and 3 patients (10%) were heterozygous mutant (GA). While in group 2, 6 patients (60%) had (GG) genotype and 4 patients (40%) were heterozygous (GA). The (AA) genotype was not detected in both groups. The comparison between both groups regarding genotype distribution showed a statistically significant difference (P=0.031), The dose of warfarin required to achieve the treatable INR in GA was 12.09 ± 2.07 and in GG was 13.16 ± 2.61 with no significant difference between them (P=0.295). Conclusion: The incidence of EPHX1 gene polymorphism (rs2292566) is higher in patients with warfarin resistance with no effect on warfarin dose in the studied population. 

Keywords: Oral anticoagulants, Warfarin resistance, EPHX1 gene.