原发性高血压患者CYP2D610不同基因型的心率震荡及美托洛尔的干预作用

Heart rate turbulence in essential hypertension patients with different genotypes of CYP2D6*10 and the intervention of metoprolol

目的：观察美托洛尔对CYP2D6＊ 10不同基因型原发性高血压患者心率震荡的影响,及原发性高血压患者CYP2D6＊ 10不同基因型对美托洛尔代谢的影响.方法：比较入选患者美托洛尔干预前后心率震荡值,又根据患者基因型被分为C/C组（39例,野生型）,T/C组（30例,突变型杂合子）和T/T组（21例,突变型纯合子）,并对美托洛尔干预后各组心率震荡值及美托洛尔血药浓度进行对比.结果：（1）与美托洛尔用药前比较,用药后患者震荡初始[TO,（-0.0742±1.46）％比（-0.864±1.62）％]显著降低,震荡斜率[TS,（3.49±3.02） ms/RR比（4.75±3.31） ms/RR]显著升高（P＜0.05～＜0.01）；与T/C组比较,C/C组,T/T组的TO值降低,TS值升高得更显著（P＜0.05）; （2） T/T组美托洛尔血药浓度明显高于C/C组和T/C组[（87.6±21.4） ng/ml比（25.6±13.3） ng/ml比（19.2±11.4） ng/ml,P＜0.01].结论：（1）美托洛尔对原发性高血压患者心率震荡有改善作用；（2） CYP2D6＊10突变纯合子型的美托洛尔血药浓度最高,突变纯合子患者心率震荡改善情况最明显.

Objective：To observe influence of metoprolol on heart rate turbulence （HRT） in patients with essential hypertension （EH） and different genotypes of CYP2D6 ＊ 10,and influence of different genotypes of CYP2D6 ＊ 10 on metoprolol metabolism in EH patients.Methods：HRT values were compared among enrolled patients before and after metoprolol intervention.According to genotype,patients were divided into C/C group （n =39,wild type）,T/C group （n=30,heterozygous mutation） and T/T group （n=21,homozygous mutation）.HRT values and blood drug level of metoprolol were compared among all groups after metoprolol intervention.Results：（1） Compared with before treatment,there was significant decrease in turbulence onset [TO,（-0.0742 ± 1.46）% vs.（-0.864 ±1.62） %] and significant increase in turbulence slope [TS,（3.49 ± 3.02） ms/RR vs.（4.75 ± 3.31） ms/RR] after treatment （P〈0.05-〈0.01） ; compared with T/C group,there was significant decrease in TO and significant increase in TS in C/C group and T/T group （P〈0.05） ; （2） Compared with C/C group and T/C group,there was significant increase in blood metoprolol level [（25.6 ± 13.3） ng/ml vs.（19.2 ± 11.4） ng/ml vs.（87.6 ± 21.4） ng/ml,P〈0.01] in T/T group.Conclusion：（1） Metoprolol can improve heart rate turbulence of patients with essential hypertension; （2） Homozygous mutation possesses most significant impact on blood metoprolol concentration,and most significant improvement effect in heart rate turbulence.