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Variants in CDHR3, CACNAC1, and LTA Genes Predisposing Sensitivity and Response to Warfarin in Patients with Cardiovascular Disease

Authors Alghamdi MA, AL-Eitan L, Alkhatib R, Al-Assi A, Almasri A, Aljamal H, Aman H, Khasawneh R

Received 22 December 2020

Accepted for publication 8 March 2021

Published 25 March 2021 Volume 2021:14 Pages 1093—1100


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Scott Fraser

Mansour A Alghamdi,1,2 Laith AL-Eitan,3 Rami Alkhatib,3 Ahmad Al-Assi,4 Ayah Almasri,3 Hanan Aljamal,3 Hatem Aman,3 Rame Khasawneh5

1Department of Anatomy, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia; 2Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia; 3Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, 22110, Jordan; 4Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 5Department of Hematopathology, King Hussein Medical Center (KHMC), Royal Medical Services (RMS), Amman, 11118, Jordan

Correspondence: Laith AL-Eitan
Department of Biotechnology & Genetic Engineering/Faculty of Science and Arts, Jordan University of Science and Technology, P.O.Box 3030, Irbid, 22110, Jordan
Tel +962-2-7201000 ext 23464
Email [email protected]

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 (rs10270308), CACNAC1 (rs216013), and LTA (rs1041981) 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

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