安徽地区汉族人群CYP2C9*3和VKORC1-1639G>A基因多态性分布及对华法林稳定剂量的影响

目的：研究CYP2C9*3及VKORC1-1639G>A基因多态性在安徽地区汉族人群中的分布情况及对患者华法林稳定剂量的影响。方法：选取安徽省5个地区6家三级综合型医院2020年1月至2021年12月1 169例患者血液样本，采用原位杂交荧光染色分析技术检测患者CYP2C9*3及VKORC1-1639G>A基因型。结果：1 169例患者CYP2C9*3基因型分布情况：AA型、AC型、CC型基因频率分别为90.16%、9.24%、0.60%；VKORC1基因型分布情况：AA型、AG型、GG型基因频率分别为84.26%、14.71%、1.03%；两基因型在患者性别、年龄及地区分布上差异无统计学意义（P>0.05）；755例达到华法林稳定剂量患者CYP2C9*3 AA基因型华法林日平均剂量（3.02±0.59）mg/d，显著高于AC与CC基因型患者（P<0.05）；VKORC1-1639AA基因型患者华法林日平均剂量（2.72±0.40）mg/d，显著低于AG与GG基因型患者（P<0.05）；达到华法林稳定剂量与未达稳定剂量患者在性别、年龄以及临床诊断上存在统计学差异（P<0.05）。结论：CYP2C9和VKORC1基因型与华法林稳定剂量有关联，以CYP2C9和VKORC1基因型为导向实施临床抗凝治疗，可为华法林个体化用药提供指导。

Distribution of CYP2C9*3 and VKORC1-1639G>A gene polymorphism in Anhui Han population and their influence on the stable dose of warfarin

AIM: To study the distribution of CYP2C9*3 and VKORC1-1639G>A gene polymorphism in Han population in Anhui province and their influence on the stable dose of warfarin. METHODS: The blood samples of 1 169 patients from 6 tertiary general hospitals in 5 areas of Anhui province from January 2020 to December 2021 were selected, the genotype of CYP2C9*3 and VKORC1-1639G>A was detected by fluorescent staining in situ hybridization technique. RESULTS: The distribution of CYP2C9*3 genotypes in 1 169 patients: the frequencies of AA, AC and CC genes were 90.16%, 9.24% and 0.60%, respectively; The distribution of VKORC1 genotype: the frequencies of AA, AG and GG genes were 84.26%, 14.71% and 1.03% respectively; There was no significant difference between the two genotypes in gender, age and regional distribution (P>0.05). The average daily warfarin dose of CYP2C9*3 AA genotype in 755 patients with stable warfarin dose was (3.02±0.59) mg/d, which was significantly higher than patients with AC genotype and CC genotype; The average daily warfarin dose of patients with VKORC1-1639AA genotype was (2.72±0.40) mg/d, which was significantly lower than that of patients with AG genotype and GG genotype (P<0.05). And the difference was statistically significant (P<0.05); There are significant differences in gender, age and clinical diagnosis between patients with stable dose of warfarin and those without stable dose (P<0.05). CONCLUSION: CYP2C9 and VKORC1 genotypes are associated with the stable dose of warfarin. Clinical anticoagulation therapy guided by CYP2C9 and VKORC1 genotypes can provide guidance for individualized medication of warfarin.