摘要
目的研究江苏徐州地区汉族人细胞色素P450(CYP)2C9和维生素K环氧化物还原酶复合体1(VKORC1)基因型与华法林剂量的关系,为华法林个体化给药方案提供建议。方法采用聚合酶链反应-连接酶检测反应(PCR-LDR)技术检测100名汉族健康受试者及200例临床使用华法林的患者CYP2C9和VKORC1基因型。结果健康受试者CYP2C9基因型中91例为*1/*1型,9例为*1/*3型;VKORC1基因型中17例为GA型,83例为AA型。200例临床使用华法林的患者CYP2C9基因型检测有179例为*1/*1型,21例为*1/*3型,未发现*2突变;VKORC1(1639G>A)基因型中168例为突变纯合子AA型,32例为杂合子GA型,未发现GG型;VKORC1(1639G>A)基因AA型患者的华法林维持剂量为(2.59±0.83)mg/d,明显低于GA型[(4.51±0.79)mg/d];CYP2C9基因*1/1*型华法林维持剂量为(3.01±1.12)mg/d,明显高于*1/*3型[(2.19±0.32)mg/d,P<0.05]。结论 CYP2C9和VKORC1基因型的多变量个体化给药方案对临床提高华法林使用的安全性有潜在的意义。
Objective To investigate the relationship of cytochrome P450 (CYP)2C9 and vitamin K epoxide reductase complex 1 (VKORC1 )genotypes with warfarin dosage,and to provide reference for the use of warfarin in Xuzhou city,Jiangsu,China.Methods A total of 1 00 Han-population healthy subjects and 200 patients with warfarin dosage were enrolled.CYP2C9 and VKORC1 genotypes were determined by polymerase chain reaction and ligase detection reaction (PCR-LDR).Results There were 91 cases of CYP2C9 genotype with *1/*1 and 9 cases of CYP2C9 genotype with*1/*3 in healthy subjects.There were 1 7 cases of VKORC1 genotype with GA and 83 cases of VKORC1 genotype with AA.VKORC1 (1639 G〉A)genotype showed homozygote AA(168 cases),heterozygote GA (32 cases)and no GG in patients with warfarin dosage GYP2C9 genotype in 200 patients had 1 79 cases of*1/*1 and 21 cases of*1/*3,and there was no*2 mutation.Warfarin dosage in VKORC1 (1 639 G〉A)in AA [(2.59 ± 0.83)mg/d]group was significantly lower than that in GA [(4.51 ±0.79)mg/d]group.Warfarin dosage in CYR2C9 genotype with *1/*9 [(3.01 ±1 .1 2)mg/d]was higher than that with*1/*3 [(2.1 9 ±0.32)mg/L,P〈0.05]. Conclusions CYP2C9 and VKORC1 genotype covariate therapy has the potential significance to improve the safety of warfarin use.
出处
《检验医学》
CAS
2014年第6期635-639,共5页
Laboratory Medicine