目的 分析細(xì)胞色素P450酶2C9（CYP2C9）和維生素K環(huán)氧化物還原酶復(fù)合體1（VKORC1）基因多態(tài)性對瓣膜置換術(shù)后華法林劑量的影響。方法 選取自2015年3月—2017年12月期間于漯河市中心醫(yī)院行瓣膜置換術(shù)后口服華法林的127例患者為研究對象。采用PCR-RFLP法分別檢測其CYP2C9和VKORC1基因型，同時記錄患者的華法林日均服用劑量、血漿總濃度及游離濃度。對不同基因型及臨床特征與華法林日常服用劑量進行直線相關(guān)及多元回歸分析。結(jié)果 華法林日均服用劑量對比，CYP2C9（1061A/C）基因型AA患者顯著高于基因型AC患者（P<0.05），VKORC1（1639 G/A）基因型AA患者顯著低于基因型AG患者（P<0.05），VKORC1（1173 C/T）基因型TT患者顯著低于基因型CT患者（P<0.05）。華法林血漿總濃度及游離濃度對比， VKORC1 （1639 G/A）基因型AA患者顯著低于基因型AG患者（P<0.05），VKORC1（1173 C/T）基因型TT患者顯著低于基因型CT患者（P<0.05）。女性患者的華法林日均服用劑量顯著低于男性患者（P<0.05），≥70歲和60～69歲患者顯著低于60歲以下各年齡段（P<0.05）。直線相關(guān)分析及多元回歸分析結(jié)果提示，華法日均服用劑量與CYP2C9、VKORC1基因型和年齡、性別相關(guān)（P<0.05）。結(jié)論 CYP2C9和VKORC1基因多態(tài)性與瓣膜置換術(shù)后華法林日常服用劑量個體化相關(guān)，同時年齡和性別也是影響因素之一。

Objective To evaluate the effects of CYP2C9 and VKORC1 Genetic Polymorphisms on Maintenance Dosage of Warfarin in Patients after Undergoing Mechanical Heart Valve Prostheses Replacement.Methods A total of 127 patients taking Warfarin after cardiac valve replacement in our hospital from March of 2015 to December of 2017 were recruited in this study, and clinical indexes such as age, gender, the average daily dose of warfarin and plasma concentration of warfarin dosage were recorded. Genotypes of CYP2C9 and VKORC1 were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and straight line correlation analysis between genotypes and clinical characteristics and multivariate logistic analysis with stable Warfarin dosage were performed. Results Maintenance dose of warfarin in patients with CYP2C9 1061A/C AA type was significantly higher than those with CYP2C9 1061A/C AC type (P<0.05). Maintenance dose of warfarin in patients with VKORC1- 1639G/A AG type was significantly higher than those with VKORC1-1639G/A AA type (P<0.05). Maintenance dose of warfarin in patients with VKORC1-1173C/T CT type was significantly higher than those with VKORC1-1173C/T TT type (P<0.05).Significant differences of plasma warfarin concentration were also observed between VKORC1-1639G/A AA and AG as well as VKORC1-1173C/T TT and CT genotypes (P<0.05), but not in those with CYP2C9 1061A/C genotypes. The average daily dose of warfarin was significantly higher in male patients than in females(P<0.05). The maintenance dose of warfarin was also significantly higher in patients under 60 years old than those aged above 60 years(P<0.05). Correlation and multivariate logistic analyses showed that there were statistically significant differences between stable Warfarin dosage with age,gender and different genotypes. Conclusion CYP2C9 and VKORC1 genotypes also have a close relationship with warfarin plasma concentration, gender and age are the important influencing factors on warfarin daily dose.