CYP2D6*10遗传基因多态性对美托洛尔在围术期保护老年患者心脏功能的影响

Effects of CYP2D6*10 genetic polymorphism on the protection of metoprolol for the elder during perioperative period

目的:探讨CYP2D6*10等位基因C188T单核苷酸多态性与美托洛尔(metoprolol,METO)在老年患者围术期心脏保护疗效的关系。方法:筛选323名应用METO预防围术期心血管风险的老年患者,采用PCR-RFLP法分析CYP2D6*10基因C188>T位点的单核苷酸多态性。患者用药后进行围术期临床跟踪,观测并评价METO治疗围术期血流动力学紊乱发生事件及个体服药后3 h肌钙蛋白的变化。结果:本研究人群中CYP2D6*10外显子C188>T位点的C、T等位基因频率分别为48.76%和51.24%,CYP2D6*10基因野生型纯合子C/C、杂合子C/T、突变型纯合子T/T基因型人群分布分别为24.76%、47.98%和27.24%,其频率分布均符合Hardy-Weinberg平衡定律。统计结果显示基因型与心血管术后均有中等强度关联。对心肌梗死风险因子的散点图按照基因多态性分布情况进行分组后分析发现,其心血管风险增高与CYP2D6*10遗传多态性存在相关的基因剂量效应。结论:CYP2D6*10基因多态性(C188>T)可能导致METO在老年患者围术期中的心脏保护功能增强,同时还可能带来心动过缓的副作用。CYP2D6*10突变与METO疗效密切相关,可致患者用药后收缩压显著改变,临床应关注CYP2D6遗传多态性对METO疗效的影响。

Objective：To investigate the relationship between CYP2D6＊10 gene C188T single nucleotide polymorphism and metoprolol efficacy in elderly patients in the perioperative cardiac protection. Methods：Totally 323 elderly patients were screened out before surgery and single nucleotide polymorphism of CYP2D6＊10gene C188＆gt;T site was analyzed by PCR-RFLP method. After metoprolol treatment,incidence of hemodynamic instability during perioperative period and changes in troponin levels at 3 hafter drug administration were observed. Results：C and T alleles frequencies were 48.76% and 51.24% in all patients,respectively.The wild-type homozygotes C/C,heterozygous C/T,mutant homozygous T/T genotype frequencies were 24.76%,47.98%,27.24%.All the frequency distribution was accord with the Hardy-Weinberg equilibrium. Statistical results showed that genotypes were moderately associated with postoperative cardiovascular surgery. CYP2D6＊10 genetic polymorphisms showed that CYP2D6 genetic polymorphism were associated with increased cardiovascular risk in a dose depended manner. Conclusion：CYP2D6＊10 gene polymorphism（C188＆gt;T）mutation may lead to reduced metabolism of metoprolol in elderly patients during the perioperative protection. CYP2D6＊10mutation and the efficacy of metoprolol is closely related,which can significantly change systolic blood pressure of patients after drug administration. Doctors should be concerned about the impact of CYP2D6 genetic polymorphism on the efficacy of metoprolol in the future.