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目的:探讨维生素K环氧化物还原酶复合物1基因(VKORC1)-1639 G/A(rs9926231)与细胞色素P450酶2C9基因(CYP2C9)1061A/C(rs1057910)多态性对中国汉族老年房颤患者华法林代谢和药效的影响。方法:用PCR-RFLP技术检测248例≥60岁房颤患者及262例≥60岁健康对照者的VKORC1-1639G/A、CYP2C9 1061 A/C基因多态性。用HPLC法检测190例口服华法林14d后国际标准化比值(INR)达标1.5～3.0患者血药浓度,比较华法林代谢的药效差异。结果:两组-1639G/A与1061A/C各基因型分布差异无统计学意义(P>0.05);INR达标组1061AA型比AC+CC型华法林维持剂量高、INR值低(P<0.05),-1639AA型比GA+GG型华法林维持剂量低(P<0.05);调整体表面积和剂量后,1061AC+CC型华法林血药浓度高于AA型(P<0.05);调整体表面积、剂量及血药浓度后,-1639AA型INR大于GA+GG型(P<0.01)。结论:对中国老年房颤患者来说,VKORC1及CYP2C9基因多态性可能影响华法林药效;VKORC1多态性可能是中国汉族人群华法林维持剂量较低的原因之一。
Objective: To investigate the effect of polymorphisms of VKORC1 -1639 G / A (rs9926231) and CYP2C9 1061A / C (rs1057910) on Chinese Han nationality elderly patients with atrial fibrillation Effects of Warfarin Metabolism and Efficacy in Patients. Methods: The polymorphisms of VKORC1-1639G / A and CYP2C9 1061 A / C in 248 patients with AF aged ≥60 years and 262 healthy controls aged≥60 years were detected by PCR-RFLP. The plasma concentrations of 190 patients with oral INR 1.5 ~ 3.0 after 14 oral warfarin oral administrations were detected by HPLC. The pharmacodynamic effects of warfarin metabolism were compared. Results: There was no significant difference in the distribution of -1639G / A and 1061A / C between the two groups (P> 0.05). The INR of 1061AA was higher than that of AC + CC warfarin and INR was lower (P < (P <0.05). The maintenance dose of 1639AA was lower than that of GA + GG warfarin (P <0.05). After the body surface area and dose were adjusted, the plasma concentrations of 1061AC + CC warfarin were higher than those of AA (P <0.05) The INR of -1639AA was higher than that of GA + GG (P <0.01) after adjusting body surface area, dosage and plasma concentration. CONCLUSIONS: VKORC1 and CYP2C9 polymorphisms may influence warfarin efficacy in Chinese elderly patients with atrial fibrillation. VKORC1 polymorphism may be one of the reasons for the low maintenance dose of warfarin in Chinese Han population.