[Polymorphisms of genes CYP2C9 and VKORC1 in patients with venous thromboembolic complications in Moscow population: effects on stability of anticoagulant therapy and frequency of hemorrhage].

Abstract To investigate frequency of carriage of genetic polymorphisms CYP2C9 and VKORC1 in patients with venous thromboembolic complications (VTEC) in Moscow population given warfarin treatment and effects of this carriage on stability of anticoagulation and frequency of hemorrhagic complications (HC) in warfarin treatment. The study included 111 patients with the history of deep vein thrombosis and/ or pulmonary artery thromboembolism. All the patients received non-fractionated or low-molecular heparin for at least 5 days, then warfarin (target INR 2.0-3.0). Warfarin dose was selected empirically. Gene CYP2C9 and VKORC1 polymorphisms were studied. HC were endpoints. Genotype CYP2C9*1/*1 (a "wild" type) was detected in 94 (84.7%) patients. Of other genotypes - heterozygotes CYP2C9*1/*2 (4.5%) and CYP2C9*1/*3 (10.8%). Genotyping by VKORC1 detected genotype GG (a wild type) in 42.3%, genotype GA--in 48.6%, genotype AA--in 9.1% patients. A mean warfarin dose, supporting an adequaite INR, was asspciated with both genotype CYP2C9 and VKORC1. Warfarin doses were highest in carriers of wile genotypes CYP2C9 and VKORC1 (6,9 and 8,8 mg/day), the lowest--in patients with genotypes CYP2C9*1/*3 and VKORC1 (4,5 and 4,0 mg/day). The carriers of polymorphisms CYP2C9*1/*3 and VKORC1 showed less stable anticoagulation vs carriers of allele variants CYP2C9*1/*1, CYP2C9*1/*2 and genotypes GG, GA VKORC1. An HC rate depended, as a rule, on carriage of genotypes CYP2C9*1/*3 and AA VKORC1. The highest risk of HC was associated with genotype CYP2C9*1/*3. The results of multifactorial regression analysis also indicated that carriage of genotype CYP2C9*1/*3, a female gender and the range of INR in warfarin treatment > or = 2,66 are independent predictors of HC in VTEC patients on warfarin treatment. Carriage of gene CYP2C9 and VKORC1 polymorphisms affects suppoting dose of warfarin and rate of hemorrhage in patients with VTEC in Moscow population. Frequency of HC is the highest in carriers of genotypes CYP2C9*1/*3 and AA VKORC1, they need minimal supporting dose of warfarin. Carriage of genotype CYP2C9*1/*3 in line with a female gender and instability of INR is an independent predictor of HC in VTEC patients in Moscow population on warfarin treatment.