CYP2C9、VKORC1基因多态性对华法令抗凝治疗维持剂量的影响

目的：研究细胞色素P4502C9基因（CYP2C9）和维生素K环氧化物还原酶复合物1基因（VKORC1）在华法令抗凝治疗患者的多态性分布，并探讨其对抗凝剂量的影响。方法：收集74例服用华法令抗凝治疗病人的外周血，测定其凝血酶原时间国际标准化比值（INR）和CYP2C9、VKORC1基因类型，探讨基因多态性的分布特点，以及华法令维持剂量与基因多态性的关系。结果：CYP2C9基因分布主要为野生型，突变型较少，抗凝治疗的维持剂量野生型组与突变组无明显差别。 VKORC1基因型的分布AA型为主，AG型较少，GG型未见，抗凝治疗的维持剂量AG组明显高于AA组。结论：CYP2C9、VKORC1基因在中国汉族人群中具有遗传多态性， VKORC1基因的多态性在华法令抗凝治疗中具有显著意义。

Effects of CYP2C9 and VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dosage of Anticoagulation

Objective： To investigate the polymorphism distribution and characteristics of cytochrome P450 2C9 （CYP2C9） and vitamin K epoxide reductase complex （VKORC1） in Han population, as well as the relationship between each polymorphism and warfarin anticoagulation dose. Methods： Seventy-four patients in Han population with stable anticoagulation taking warfarin were recruited. Their CYP2C9 and VKORC1 genotypes were tested by pyrosequencing, and their international normalized ratios （INR） were obtained. Re_sults： Most of the patients in our study had wild type CYP2C9, with similar warfarin doseage to those of mutated type. For VKORC1 genotype, most patients with wild type AA had lower warfarin doseage than those with the mutated variant. Conclusion： The genetic polymorphisms of CYP2C9 and VKORC1 present in Han population, and the VKORC1 genotypes could affect individualized warfarin dose in anticoagulation.