title: CYP2C9 and VKORC1 genetic polymorphism analysis might be necessary in patients with Factor V Leiden and prothrombin gene G2021A mutation(s).
abstract: The annual incidence of venous thromboembolism is approximately 117 per 100,000 persons or about 1 per 1000 person-years, with the majority of the disease occurring in the older age groups. Factor V Leiden gene (most common) and the prothrombin G20210A gene mutation are inherited mild to moderate risk factors for hypercoagulability. The anticoagulant warfarin requires close monitoring of the patient's prothrombin time, normalized as the international normalization ratio. Patients with either Cytochrome P-450 CYP2C9*2, CYP2C9*3, or VKORC1*2 genotype (c.-1639G>A) require significantly reduced doses, and are at a higher risk of serious bleeding. Thirty-five samples in total, 15 with Factor V Leiden, 18 with prothrombin G2021A mutation, and 2 with both were analyzed for 2C9*2, 2C9*3, and VKORC1 (-1639) allele variants by using the Invader CYP2C9 and VKORC1 polymorphism analysis kit. Eight with CYP2C9*2 C/T, 2 with CYP2C9*3 A/C, 5 with VKORC1 (-1639) A/A, and 22 with VKORC1 (-1639) G/A genotypes or 29 out of 35 (83%) samples analyzed were found with CYP2C9*2 C/T, CYP2C9*3 A/C, VKORC1 (-1639) G/A, or/and VKORC1 (-1639) A/A genotypes. CYP2C9*2 C/T, CYP2C9*3 A/C, VKORC1 (-1639) G/A genotyping might be necessary for patients with Factor V Leiden and/or prothrombin G2021A mutation before warfarin anticoagulant therapy.
authors.affiliation: Molecular Pathology Laboratory, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
authors.forename: Allen
authors.initials: A
authors.lastname: Leung
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Huang
authors.forename: Riho
authors.initials: R
authors.lastname: Muto
authors.forename: Yinxian
authors.initials: Y
authors.lastname: Liu
authors.forename: Qiulu
authors.initials: Q
authors.lastname: Pan
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D025861:Blood Coagulation Disorders, Inherited / Q000188:drug therapy* / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005165:Factor V / Q000235:genetics; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; C095381:factor V Leiden; D014859:Warfarin; D005165:Factor V; D011516:Prothrombin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases