基于基因多态性初步分析华法林的使用

Application Analysis of Warfarin Based on Genetic Polymorphism

基于VKORC1-1639 G/A及CYP2C9~*3的基因多态性初步探讨华法林的使用,收集2016年10月2018年2月至该院进行华法林用药指导相关基因检测的100例患者,记录患者基本信息(身高、体重等)。采用数字荧光分子杂交(DFMH1)检测VKORC1-1639 G/A,CYP2C9~*3的基因型分布,并结合患者年龄、身高、体重等,根据国际华法林药物基因组学联合会(IWPC)公式计算患者华法林初始剂量。VKORC1-1639 G/A AA、AG、GG基因型实际频率分别为84%,15%,1%;等位基因频率A(91. 5%),G(8. 5%)。CYP2C9~*3 AA型、AC型、CC型实际频数分别为91%,9%,0%;等位基因频率A(95. 5%),C(4. 5%)。不同VKORC1-1639 G/A、CYP2C9基因型华法林用量不同,VKORC1-1639 G/A AA型并CYP2C9~*1/~*1型和VKORC1-1639 G/A AG型并CYP2C9~*1/~*1型患者华法林剂量均高于VKORC1-1639 G/A AA型并CYP2C9~*1/~*3型患者; VKORC1-1639 G/A AG型并CYP2C9~*1/~*1型患者华法林用量高于VKORC1-1639 G/A AA型并CYP2C9~*1/~*1型患者,3组比较,差异有统计学意义(P <0. 05)。华法林代谢相关基因的基因多态性为VKORC1-1639 G/A AA及CYP2C9~*1/~*1型占多数,表明VKORC1-1639 G/A基因突变率高,CYP2C9~*3基因突变率低,且其多态性影响个体间华法林的使用剂量,但不同性别个体间华法林初始剂量大致为3 mg/d。

Investigating the use of warfarin on the basis of gene polymorphisms of vkorc1-1639 g/A and CYP2C9*3,collecting from October 2016 to February 2018 to Yan’an hospital for warfarin guidelines related to genetic testing of 100 patients and recording patients basic information(height,weight,etc.).The genotype distribution of vkorc1-1639 g/A and CYP2C9*3 was detected by digital fluorescent molecular hybridization(DFMH1),and the initial dose of warfarin was calculated according to the formula of international warfarin pharmacogenomics federation(IWPC)combined with the patient’s age,height and weight.The actual frequencies of vkorc1-1639 G/A AA,AG and GG genotypes were 84%,15%and 1%respectively.Allele frequencies A(91.5%)and G(8.5%).The actual frequencies of CYP2C9*3 AA,AC and CC were 91%,9%and 0%respectively.Allele frequencies A(95.5%)and C(4.5%).Different vkorc1-1639 g/A,CYP2C9 genotype warfarin dosage was different,vkorc1-1639 g/A AA type,CYP2C9*1/*1 type and vkorc1-1639 g/A AG type,warfarin dosage was higher than that of vkorc1-1639 g/A AA type and CYP2C9*1/*3 type.Warfarin dosage was higher than that of vkorc1-1639 G/A AA type in patients with cyp2 c1-1639 G/A type 1 and cyp2 c1-1639 G/A type 1,and the differences were statistically significant(P<0.05).The majority of warfarin metabolic related genes were vkorc1-1639 G/A AA and CYP2C9*1/*1 type,indicating high mutation rate of vkorc1-1639 G/A.The mutation rate of CYP2C9*3 is low,and its polymorphism affects the dose of warfarin among individuals.However,the initial dose of warfarin between different genders was about 3 mg/d.