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目的:探讨VKORC1 1173C>T基因多态性位点与个体间华法林稳定剂量差异的关系。方法:采用实时荧光PCR结合熔解曲线分析的方法,检测323例已获得华法林稳定剂量患者的VKORC1 1173C>T位点基因型;比较不同基因型患者的华法林稳定剂量的差异。结果:贵州汉族和少数民族的VKORC1 1173C>T基因型和等位基因频率分布差异无统计学意义。323例患者中,VKORC1 1173C>T基因型TT、TC和CC分别有253例、66例和4例,各占78.3%、20.4%和1.2%,等位基因T和C的频率分别为88.5%和11.5%。在VKORC1的3种基因型中,TT基因型组剂量最低(2.58±0.78)mg/d,与TC组(4.25±1.35)mg/d和CC组(4.53±0.94)mg/d比较有显著性差异(P<0.001)。结论:VKORC1 1173C>T基因多态性是影响华法林个体间用量差异的一个主要遗传因素,对患者的VKORC1 1173C>T位点进行分型,可作为华法林个体化用药的一个重要依据。
Objective: To investigate the relationship between VKORC1 1173C> T polymorphism and individual warfarin dose stability. Methods: The genotypes of VKORC1 1173C> T locus in 323 patients with stable warfarin dose were detected by real-time fluorescence PCR combined with melting curve analysis. The difference of warfarin dosage in different genotypes was compared. Results: There was no significant difference in the frequency distribution of VKORC1 1173C> T genotypes and alleles in Guizhou Han and ethnic minorities. Among 323 patients, TT, TC and CC of VKORC1 1173C> T genotype were 253 cases, 66 cases and 4 cases, accounting for 78.3%, 20.4% and 1.2%, respectively. The frequencies of allele T and C were 88.5% And 11.5%. Among the three genotypes of VKORC1, TT genotype had the lowest dose (2.58 ± 0.78) mg / d, which was significantly lower than that of TC (4.25 ± 1.35) mg / d and CC (4.53 ± 0.94) mg / d Difference (P <0.001). CONCLUSION: VKORC1 1173C> T polymorphism is a major genetic factor influencing warfarin dosage differences. Typing VKORC1 1173C> T loci in patients may be an important basis for individualized warfarin use .