华法林相关基因CYP2C9、VKORC1、CYP4F2的多态性分布

Polymorphism distribution of warfarin-related genes VKORC1,CYP2C9 and CYP4F2

目的研究CYP2C9、VKORC1、CYP4F2基因多态性在陕西省宝鸡地区汉族人群中的分布情况,为华法林个体化用药提供遗传依据。方法选取2022年1月至2023年5月在宝鸡市中医医院心内科接受华法林治疗并进行相关基因检测的住院患者475例,采用飞行时间质谱仪对华法林药物相关基因CYP2C9、VKORC1、CYP4F2分别进行检测,然后对检测结果的基因多态性进行分析。结果华法林药物相关各基因分布频率符合Hardy-Weinberg equilibrium规律,475例患者VKORC1基因型分别是AA型、AG型、GG型,基因频率分别为83.79%,15.58%,0.63%;CYP2C9基因型分别是*1/*1型、*1/*3型、*1/*2型,基因频率分别为95.17%,4.74%,0.11%,未检出*2/*2、*2/*3、*3/*3基因型;CYP4F2基因型分别是*1/*1型、*1/*3型、*3/*3型,基因频率分别为52.40%,39.37%,8.21%。各基因型分布在患者不同性别、年龄之间无统计学差异。结论陕西宝鸡地区汉族人群华法林药物基因VKORC1(c.-1639G>A)以变异型为主,包括纯合变异和杂合变异,而CYP2C9(*1、*2、*3)和CYP4F2(*1,*3)以野生型为主。

Objective To investigate the distribution of CYP2C9,VKORC1 and CYP4F2 gene polymorphisms in Han population in Baoji in Shaanxi province,and provide genetic basis for the personalized use of warfarin.Methods A total of 475 hospitalized patients who received warfarin treatment in the department of cardiology in Baoji City Hospital of Traditional Chinese Medicine from January 2022 to May 2023 were selected.The three genes related to warfarin drugs,CYP2C9,VKORC1 and CYP4F2,were detected by time-of-flight mass spectrometer and then the genetic polymorphism was analyzed.Results The distribution frequency of each gene was in line with Hardy Weinberg equilibrium.The VKORC1 genotypes of 475 patients were AA,AG and GG,and the gene frequencies were 83.79%,15.58%and 0.63%,respectively.CYP2C9 genotypes were*1/*1,*1/*3 and*1/*2,with gene frequencies of 95.17%,4.74%and 0.11%,respectively,and*2/*2,*2/*3 and*3/*3 genotypes were not detected.The CYP4F2 genotypes were*1/*1,*1/*3 and*3/*3,and the gene frequencies were 52.40%,39.37%and 8.21%,respectively.There was no significant diffe-rence in the distribution of genotypes among patients with different genders and ages.Conclusion In the Han population in Baoji area of Shaanxi province,warfarin drug-related gene VKORC1(c.-1639G>A)is chiefly predominated by mutant variants,including homozygous variants and heterozygous variants,while CYP2C9(*1,*2,*3)and CYP4F2(*1,*3)is chiefly wild typed.