title: VKORC1 and CYP2C9 genotypes in Egyptian patients with warfarin resistance.
abstract: Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15 mg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20 mg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with P ≤ 0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (P = 0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.
authors: aDepartment of Clinical Pathology bDepartment of Vascular Surgery cDepartment of Public Health, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Hanan
authors: H
authors: Azzam
authors: Hossam
authors: H
authors: Elwakeel
authors: Ibrahim
authors: I
authors: Awad
authors: Reham
authors: R
authors: El-Farahaty
authors: Abdel-Hady
authors: AH
authors: El-Gilany
authors: Solafa
authors: S
authors: El-Sharawy
mesh_terms: D000328:Adult; D000483:Alleles; D000925:Anticoagulants / Q000627:therapeutic use*; D018912:Arabs; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004334:Drug Administration Schedule; D004534:Egypt; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases