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目的 研究维生素K环氧化物还原酶复合体亚单位1(VKORC1)基因和细胞色素P450 2C9(CYP2C9)基因的多态性、临床特征及其与肥厚型心肌病患者应用华法林稳定剂量、出血并发症及抗凝过度的相关性.方法 选取2011年1月至2016年12月辽宁省人民医院心血管内科收治的明确诊断为肥厚型心肌病(HCM)及房颤并规律口服华法林抗凝的患者60例,记录患者年龄、身高、体质量、华法林稳态剂量、是否曾出现抗凝过度及出血并发症等临床特征,采用荧光PCR-毛细管电泳测序法对VKORC1及CYP2C9基因进行检测,使用统计学方法对各基因型及临床特征与华法林稳定剂量、出血并发症及抗凝过度的相关性进行分析.结果 60例患者中,VKORC1-1639G>A检测有AA型50例、AG型9例、GG型1例,AA型华法林稳定剂量较AG型低,差异有统计学意义(P<0.05),携带A等位基因不增加出血及抗凝过度风险,差异无统计学意义(P>0.05);CYP2C9检测中*1/*1型51例,*1/*3型6例,*3/*3型3例,未检测到*2突变,携带*3突变者华法林稳定剂量较*1/*1型低,且所携带*3突变越多稳定剂量越低,差异有统计学意义(P<0.05),携带*3等位基因不增加出血及抗凝过度风险,差异无统计学意义(P>0.05).年龄≥65岁患者出血及抗凝过度发生率显著高于年龄<65岁患者,差异有统计学意义(P<0.05).结论 HCM患者应用华法林稳定剂量与VKORC1和CYP2C9基因多态性有关,年龄可能是华法林出血并发症及抗凝过度的影响因素.

Objective To investigate the gene polymorphisms and clinical features of vitamin K epoxide reductase complex 1(VKORC1) and cytochrome P450 2C9(CYP2C9),and their correlation with stable dosage of warfarin,the risk of hemorrhage and over anticoagulation for patients with hypertrophic cardiomyopathy.Methods A retrospective study was performed on 60 patients with hypertrophic cardiomyopathy(HCM) combined with atrial fibrillation(AF) who were admitted and regularly took oral warfarin as anticoagulation from January 2011 to December 2016.The clinical data such as age,body height,body weight,stable warfarin dosage and the situation of hemorrhage and over anticoagulation were recorded.Genotypes of CYP2C9 and VKORC1 were detected with fluorescence PCR-capillary electrophoresis sequencing and the relationship between the genotype and clinical features and the stable dose of warfarin,hemorrhage and over anticoagulation were analyzed by statistical methods.Results Among the 60 patients,VKORC1-1639G>A detection showed that 50 patients were AA type,9 patients were AG type,1 patient was GG type,the stabledosage of AA type patients were significant lower than that of AG type patients(P<0.05),the correlation between the polymorphisms of VKORC1 with the risk of hemorrhage and over anticoagulation was not found(P>0.05);CYP2C9 detection showed that 51 patients were *1/*1 type,6 patients were *1/*3 type,3 patients were *3/*3 type,*2 allele was not found,the stable dosage of patients who carry the *3 mutation were significant lower than that of *1/*1 type patients,and the more *3 mutation they own,the lower dosage they require(P<0.05),the correlation between the polymorphisms of CYP2C9 with the risk of hemorrhage and over anticoagulation was not found(P>0.05).The incidence of hemorrhage and anticoagulation was significantly higher in patients aged 65 years or older than those who were younger than 65 years(P<0.05).Conclusion Stable warfarin dosage has relationship with different genotypes of VKORC1 and CYP2C9 in HCM patients,age may be a factor of warfarin over anticoagulation and hemorrhage.