1. Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.
2. Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.
3. Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
4. Department of Hematopathology, King Hussein Medical Center (KHMC), Royal Medical Services (RMS), Amman 11118, Jordan.
5. Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabi.
6. Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia.
Cardiovascular diseases are among the leading causes of death worldwide. Many of those diseases require treatment with warfarin, an anticoagulant that has a large high inter and intra-variability in the required doses. The aim of this study is to find if there are any associations between rs2108622 of CYP4F2, rs7412 and rs405509 of ApoE, and rs1801272 of CYP2A6, and CVD and warfarin dose variability. The selected genes and their polymorphisms are involved in many GWAS associated with cardiovascular disease and variability in warfarin treatment. The study sample consisted of 212 Jordanian Cardiovascular patients and 213 healthy controls. DNA was extracted and the Mass ARRAY™ system was used to genotype four selected SNPs within three genes (CYP4F2, ApoE, and CYP2A6). Only one out of the four selected SNPs (ApoE rs7412 SNP) was found to be associated with the risk of cardiovascular disease. Also, this SNP showed significant differences in warfarin initial doses. CYP2A6 rs1801272 SNP was found to be associated with warfarin sensitivity during the initiation phase of therapy and with warfarin responsiveness and INR measurement during the stabilization phase of therapy. This study improves the current understanding of the high inter and intra-variabilities in response to warfarin, including the variety of dosing requirements and the susceptibility to cardiovascular disease in the Jordanian Arab population. Further study on a larger sample and in different ethnic groups could help in improving our understanding of warfarin's pharmacogenetics and its application in personalized medicine.
Keywords: Warfarin, cardiovascular disease, APOE, CYP4F2, and CYP2A6