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This study aimed to find the correlation between genotypes of CYP4F2 and bleeding events in warfarin treatment patients.
We recruited consecutive patients who use warfarin for the first time in Chinese PLA General Hospital. All included patients should be aged ≥ 18 years, prescribed with warfarin for at least 3 months. Demographic characteristics and clinical information were recorded. Follow-up visits were scheduled every 1 week in 3 months for bleeding complications monitoring, which assessed using the Fihn criteria. We genotyped eight tag SNPs (rs7251296, rs4808394, rs12610962, rs3093168, rs2074901, rs2018454, rs1558139 and rs3093200) in CYP4F2. CYP2C9*3, VKORC1-1639 G>A, and CYP4F2 V433M were also genotyped. The association of the tag SNPs and the risk of bleeding complications was evaluated using Cox proportional hazard regression with adjustment for potentially confounding variables.
Among the genotyped 459 patients (mean age, 57 ± 15 years; 54.5% men), a total of 17 major and 79 minor bleeding complications occurred over 3 months. The incidence for major bleeding complications in this cohort was 3.7%, similar to those reported previously. Of all the tested CYP4F2 polymorphisms, only the SNP rs3093168 was statistically associated with major bleeding complications. The incidence rate of major bleeding complications was significantly higher among patients with CC alleles (7.02%) than those with the CG and GG alleles (2.61%) (HR：3.63; 95%CI: 1.23-10.72; P=0.019). No significant correlation was found between any of the CYP4F2 genotypes and the minor bleeding events. All the major bleeding complications in the patients with rs3093168 CC genotype occurred after the stabilization of warfarin anticoagulation.
The patients with rs3093168 CC alleles have a significantly higher incidence rate of major bleeding complications, for these patients, more attention needed to achieve a more safe and effective anticoagulant effect.