CYP2C9和VKORC1基因多态性对高龄非瓣膜性心房颤动病人华法林维持剂量的影响  

Effects of CYP2C9 and VKORC1 gene polymorphisms on maintenance dosage of warfarin in patients aged 80 years old with non-valvular atrial fibrillation

作　　者：王森 门琛 吴军 许健 郭妍 WANG Sen;MEN Chen;WU Jun;XU Jian;GUO Yan(Department of Geriatric Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院老年心血管科,江苏省南京市210029

出　　处：《实用老年医学》2020年第4期360-363,共4页Practical Geriatrics

摘　　要：目的探讨细胞色素P450(CYP)2C9与维生素K环氧化物还原酶复合物1(VKORC1)基因多态性对高龄非瓣膜性心房颤动病人华法林维持剂量的影响。方法选取40例≥80岁非瓣膜性心房颤动病人为研究对象,记录病人的性别、年龄及华法林稳定给药剂量。采用数字荧光分子杂交测序技术检测病人的CYP2C9及VKORC1基因型,根据国际华法林药物基因组联合会(IWPC)公式计算出病人的华法林服用理论剂量。结果男性病人与女性病人的华法林日均剂量差异无统计学意义[(2. 16±0. 75)mg比(2. 00±0. 47)mg,P> 0. 05]。CYP2C9-1075 A/C基因型中,AA型33例,CA型7例;AA型病人的华法林理论剂量明显高于CA型病人(P <0. 01);但两者的实际用量差异无统计学意义(P=0. 601)。VKORC1-1639 A/G基因型中,AA型33例,GA型7例;GA型病人的华法林理论剂量和实际用量均明显高于AA型病人(P <0. 05)。CYP2C9-1075 AA+VKORC1-1639 GA基因型病人的华法林实际用量明显高于CYP2C9-1075 CA+VKORC1-1639 AA基因型病人(P <0. 05),但其他组合基因型的华法林实际用量差异均无统计学意义(P> 0. 05)。结论 VKORC1基因多态性是影响高龄老人华法林维持剂量的重要遗传因素,可根据病人基因型的不同合理分配华法林剂量。Objective To investigate the effect of cytochrome P450(CYP)2C9 and vitamin K epoxide reductase subunit 1(VKORC1)gene polymorphisms on maintenance dosage of warfarin in the patients aged ≥ 80 years old with non-valvular atrial fibrillation(nvAF). Methods A total of 40 patients aged ≥ 80 years old were enrolled in the study. The sex,age and warfarin stable dose were recorded. The CYP2C9 and VKORC1 genotypes of the patients were detected by digital fluorescence molecular hybridization sequencing technology,and the theoretical dose of warfarin was calculated according to the algorithm of International Warfarin Pharmacogenomics Consortium(IWPC). Results There was no significant difference in warfarin stable dose between different genders(P > 0. 05). 33 cases presented with CYP2C9-1075 AA type and 7 cases with CA type;The theoretical dose of warfarin in AA type was significantly higher than that in CA type(P < 0. 05),but warfarin stable dose showed no significant difference(P=0. 601). 33 cases presented with VKORC1-1639 AA type and 7 cases with GAtype;The theoretical and stable dose of warfarin in GA type were significantly higher than those in AAtype(P < 0. 05). The warfarin stable dose of the patients with CYP2C9-1075 AA and VKORC1-1639 GA genotypes was significantly higher than that of the patients with CYP2C9-1075CA and VKORC1-1639 AA genotypes(P < 0. 05),however,there was no significant difference among the other genotypes(P > 0. 05). Conclusions VKORC1 gene polymorphism is an important genetic factor which would affect the warfarin stable dose in the elderly aged ≥ 80 years old.

关 键 词：老年人 心房颤动 维生素K环氧化物还原酶复合物1 细胞色素P4502C9 华法林 

分 类 号：R541.75[医药卫生—心血管疾病]