摘要
目的探讨重庆地区人工机械瓣膜置换术后华法林抗凝治疗患者CYP2C9*1和*3基因型与华法林口服剂量及稳定华法林血药浓度的关系。方法采用PCR-RFLP技术对100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者CYP2C9*1和*3基因突变位点进行检测,计算其基因型和等位基因频率;采用高效液相色谱法(HPLC)测定患者血浆中华法林浓度,同时记录患者相关临床指标。结果 100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者中筛选到2种基因型:CYP2C9*1/*1及CYP2C9*1/*3,基因型频率分别为95%和5%,未发现CYP2C9*2基因型及CYP2C9*3/*3型纯合子患者。在达到抗凝指标INR(1.5~2.0)后,CYP2C9*1/*3型患者需要的华法林维持剂量(2.67±0.95)mg与CYP2C9*3/*3型患者需要的华法林维持剂量(2.67±1.10)mg相比无明显差别(P>0.05),而前者稳定华法林血药浓度(1640.95±287.89)ng/ml与后者(805.50±329.77)ng/ml相比有明显差别(P<0.01)。结论 100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者CYP2C9*1和*3基因型与相应的患者的华法林口服剂量个体差别无相关。CYP2C9*1和*3基因型与术后抗凝治疗患者达到抗凝稳定状态后的华法林血药浓度个体差异相关,CYP2C9*1和*3基因型筛查对监测华法林药物抗凝并发症有重要意义。
Objective To study the correlation between CYP2C9 * 1 and * 3 mutations and Warfarin dosage in patients after replacement of mechanical heart valve in Chongqing area.Methods CYP2C9* 1 and * 3 mutations were detected in 100 patients after replacement of mechanical heart valve by PCR-RFLP.Mutation frequencies of CYP2C9* 1 and * 3 genes and allelic genes were calculated.Two Warfarin concentrations were measured in the patients by HPLC with related clinical parameters recorded.Results Two genotypes,CYP2C9* 1 /* 1 and CYP2C9* 1 /* 3,were detected in the patients after treatment with Warfarin in Chongqing area,with a frequency of 95% and 5%,respectively.No CYP2C9* 2 and CYP2C9* 3 /* 3 were detected.After INR reached 1.5-2.5,the patients with CYP2C9* 1 /* 3 and CYP2C9* 3 /* 3 were treated with Warfarin at maintenance dose of(2.67 ± 0.95) mg and(2.67 ± 1.10) mg,respectively(P 0.05).The stable Warfarin concentration was(1 640.95 ±287.89) ng/ml for patients with CYP2C9* 1/* 3 and(805.50 ± 329.77) ng/ml for those with CYP2C9* 3 /* 3(P 0.01).Conclusion The dose of Warfarin is not related with CYP2C9 * 1 and * 3 mutations in patients after replacement of mechanical heart valve.However,the stable Warfarin concentration is related with CYP2C9* 1 and * 3 mutations in patients after replacement of mechanical heart valve.Detection of CYP2C9* 1 and * 3 mutations is of great importance in predicting the complications of anticoagulation treatment with Warfarin.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第19期2089-2093,共5页
Journal of Third Military Medical University