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目的:调查广州地区汉族人群与华法林代谢相关的CYP2C9/VKORC1基因多态性分布特征,并了解经验用药患者与根据基因型进行个体化抗凝治疗患者凝血指标(TT、PT、PT-INR、FIB)的改变。方法:选取2015年1月至12月住院或门诊676例患者,采用基因芯片法进行CYP2C9/VKORC1基因多态性检测,分析基因型频率和等位基因频率,了解广州地区汉族人群CYP2C9/VKORC1基因多态性分布特征和凝血情况。随机选取初期2.5~3 mg·d-1经验用药组(A组)服用华法林患者91例;经验用药一段时间后进行了CYP2C9/VKORC1基因多态性检测,并根据基因型行个体化用药(B组)。2组患者均按要求定期检测凝血指标。结果:广州地区汉族人群CYP2C9/VKORC1基因型*1*1/AA占74.567%;*1*1/GA占16.57%;*1*3/AA占6.21%;*1*3/GA和*1*1/GG各占1.18%;*1*2/AA和*1*3/AA各占0.15%。凝血指标(TT、PT、PT-INR、FIB)A组依次为(13.97±1.43)s、(16.74±8.34)s、(1.47±0.77)INR、(3.34±0.90)s,B组依次为(13.76±1.17)s、(21.71±11.40)s、(1.96±0.90)INR、(3.63±0.92)s;经配对资料t检验,TT2组间无显著差异(P>0.05);PT和PT-INR2组间均有非常显著差异(P<0.01);FIB A组与B组间有显著差异(P<0.05)。A组、B组患者在治疗过程中PTINR控制在2~3 INR抗凝治疗理想范围的分别占13.6%和23.57%,经χ2检验有显著差异(P<0.05)。结论:广州地区汉族人群CYP2C9/VKORC1呈基因多态性,因此华法林按传统经验用药抗凝治疗模式存在一定的盲目性和潜在的危险性,以基因为导向的个体化抗凝治疗为临床在调整华法林抗凝治疗方案提供了科学依据,减少不良事件的发生率。
Aims: To investigate the distribution of CYP2C9 / VKORC1 polymorphisms in warfarin metabolism in Han Chinese population in Guangzhou and to investigate the relationship between the level of CYP2C9 / VKORC1 polymorphism and the blood coagulation index (TT, PT, PT-INR , FIB) changes. Methods: Six hundred and seventy-six inpatients or outpatients from January 2015 to December 2015 were enrolled in this study. CYP2C9 / VKORC1 gene polymorphism was detected by gene chip method. Genotype frequency and allele frequency were analyzed to understand the CYP2C9 / VKORC1 gene in Guangzhou Han population Polymorphism distribution and coagulation status. Ninety-one patients were randomized to receive warfarin in the initial 2.5-3 mg · d-1 experimental group (A group). CYP2C9 / VKORC1 gene polymorphism was tested after a period of empirical medication and genotyped with individualized medication (Group B). Patients in both groups were regularly tested for clotting indicators as required. Results: The genotypes of CYP2C9 / VKORC1 in Han population in Guangzhou were 74.567%, * 1 * 1 / GA and 16.57%, respectively. * 1 * 3 / AA accounted for 6.21% * 1 / GG 1.18% each; * 1 * 2 / AA and * 1 * 3 / AA each 0.15%. The indexes of coagulation index in group A were (13.97 ± 1.43) s, (16.74 ± 8.34) s, (1.47 ± 0.77) INR, (3.34 ± 0.90) s in group A and There was no significant difference between TT2 group (P> 0.05), PT and PT-INR2 (13.76 ± 1.17) s, (21.71 ± 11.40) s, (1.96 ± 0.90) INR, There was significant difference between the two groups (P <0.01). There was significant difference between FIB group and B group (P <0.05). Patients in group A and group B had 13.6% and 23.57% PTINR control within the range of 2 to 3 INR anticoagulant therapy respectively, which was significantly different by χ2 test (P <0.05). CONCLUSIONS: CYP2C9 / VKORC1 is a genetic polymorphism in Han population in Guangzhou. Therefore warfarin is blind and potentially dangerous in the traditional empirical anticoagulant therapy. Gene-oriented and personalized anticoagulant therapy is clinically Adjust the warfarin anticoagulation regimen provides a scientific basis to reduce the incidence of adverse events.