Genetic modulation of oral anticoagulation with warfarin

Cytochrome P450 CYP2C9 gene variants have been associated with hyperrespons iveness to small doses of warfarin and a higher bleeding complication rate. The aim of this study was to investigate whether CYP2C9 gene variants affe ct doses of drug prescribed to acquire the target anticoagulation intensity and the occurence of bleeding complications. in a cohort of 180 patients f ollowed up at one specialized clinic from the start of the anticoagulation with warfarin, we have investigated whether CYP2C9 gene variants have affec ted doses of drug prescribed to acquire the target anticoagulation intensit y and the incidence of bleeding complications. The adjusted dose required of warfarin was higher among patients with the C YP2C9*1 haplotype (5.6 mg) than those of patients carrying the CYP2C9*2 (4. 7 mg; p = 0.007, Scheffe's test) or the CYP2C9*3 haplotype (4.0 mg; p <0.00 1, Scheffe's test). The occurrence of bleeding complications was more frequ ent among patients with the CYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of the CYP2C9*1 haplotype (OR: 2.57; 95% CI: 1.16-5.73). An intera ction between the presence of local bleeding sources and the CYP2C9*2 and/o r the CYP2C9*3 haplotype was observed (p <0.001). Patients with both local sites of potential bleeding and CYP2C9*2 and/or the CYP2C9*3 haplotype had the higher estimated risk of bleeding (OR: 12.81; 95% CI: 2.86-57.26). CYP2C9 gene variants modulate the anticoagulant effect of the dose of warfa rin prescribed. The incidence of bleeding complications in CYP2C9*2 and CYP 2C9*3 carriers was significantly higher than that in noncarriers and intera cted with the presence of local bleeding sources.