Variants in CDHR3, CACNACI, and LTA Genes Predisposing Sensitivity and Response to Warfarin in Patients with Cardiovascular Disease

Introduction: Warfarin has been in use for more than 60 years; however, it has serious side effects including major bleeding. The high interpatient variability in the required dose impacts the sensitivity and responsiveness to warfarin in different patients. This study aims to assess the influence of CDHR3, CACNAC1, and LTA gene polymorphisms on the variability of warfarin dose requirements and susceptibility to coronary heart disease in the Jordanian population. Methods: This study was conducted in the anti-coagulation clinic in Queen Alia Heart Institute in Amman, with 212 patients in total. Three SNPs were genotyped within CDHR3 (rsl0270308), CACNAC1 (rs216013), and LTA (rsl041981) genes. Results: Our findings revealed that patients with LTA polymorphism are more prone to warfarin sensitivity than others. Furthermore, carriers of the LTA polymorphism needed a lower initial dose of warfarin and are associated with less variation in doses required to achieve target INR. Conclusion: The current study could help in understanding the role of genetic variability in warfarin dosing and matching patients to different treatment options. Clinical applications of these findings for warfarin treatment may also contribute to improving the efficacy and safety of warfarin treatment in Jordanian patients with cardiovascular disease. Keywords: warfarin, pharmacogenetics, single nucleotide polymorphisms, INR, stroke