CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系

摘要

Objective:To study the relationship betWeen CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension.Methods:A total of 60 patients With essential hypertension (EH)received metoprolol 47.5mg/d for 3d.After 3d the plasma metoprolol concentration after oral 2h Was measured.Polymorphism of CYP2D6*10 gene Was detected by PCR-RFLP.According to results of gene detection,the patients Were divided in-to CC genotype group (Wild type homozygote,fast metabolism type,n=14),CT genotype group (heterozygous mu-tation,intermediate metabolism type,n=25)and TT genotype group (homozygous mutation,sloW metabolism,n=19).Metoprolol dosage Was adjusted according to CYP2D6*10 genotype.After one Week,plasma concentration of metoprolol after oral 2h Was measured again,and mean heart rate and blood pressure Were measured before and af-ter gene-directed therapy.Results:Before gene-directed therapy,compared With CC and CT group there Was signif-icant increase in plasma concentration of metoprolol [(26.57±19.40)ng/ml vs.(23.88±12.86)ng/ml vs.(64.74 ±32.94)ng/ml,P<0.01]in TT group;compared With TT group,there Were significant rise in mean systolic blood pressure [mSBP,(132.84±13.40)mmHg vs.(144.14±14.28)mmHg],mean diastolic blood pressure [mD-BP,(76.95±9.07)mmHg vs.(81.36±7.33)mmHg]and mean heart rate [mHR,(69.13±11.83)times/min vs. (76.66±7.33)times/min]in CC group,P<0.05 all.After gene-directed therapy,there Were no significant differ-ence in plasma concentration of metoprolol,mSBP,mDBP and mHR among all groups,P>0.05 all;Compared With before gene-directed therapy,there Was significant increase in plasma concentration of metoprolol,and signifi-cant decrease in mSBP,mDBP and mHR in CC group (P<0.05).There Were no significant difference in blood pressure and heart rate betWeen before and after treatment in CT group and TT group (P>0.05 ).Conclusion:CYP2D6*10 gene polymorphism affects metoprolol metabolism and its therapeutic effect on hypertension,gene-di-rected therapy can significantly improve drug therapeutic effect and reach ideal therapeutic goal in short time.%目的：研究CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系。方法：60例原发性高血压患者口服美托洛尔47.5 mg/d三日后，测定口服美托洛尔2h 的血药浓度。应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测CYP2D6*10基因型，根据基因检测结果高血压病人被分为 CC型组（野生型纯合子，快代谢型，14例），CT型组（突变杂合子，中代谢型，25例）和 TT型组（突变纯合子，弱代谢性，19例）3组。根据CYP2D6*10基因型调整美托洛尔用量，一周后，再次检测口服美托洛尔2h的血药浓度，并检测基因导向治疗前后的平均心率及血压。结果：基因导向治疗前，美托洛尔血药浓度 TT组显著高于 CC和 CT组[（64.74± ；32.94）ng/ml比（26.57±19.40）ng/ml比（23.88±12.86）ng/ml，P＜0.01]；与 TT组比较，CC组平均收缩压[（132.84±13.40）mmHg比（144.14±14.28）mmHg]、舒张压[（76.95±9.07）mmHg比（81.36±7.33） mmHg]、心率[（69.13±11.83）次/min比（76.66±7.33）次/min]明显升高（P 均＜0.05）。基因导向治疗后各组的血药浓度、平均收缩压、舒张压及心率无统计学差异（P 均＞0.05）。与基因导向治疗前比较，CC组治疗后血药浓度显著升高，平均收缩压、舒张压及心率显著降低（P＜0.05）， CT组、TT组的血压及心率与治疗前比较无统计学差异（P＞0.05）。结论：CYP2D6*10基因多态性影响美托洛尔药物代谢及其治疗高血压病的疗效，基因导向个体化治疗可显著改善疗效，短时间内达到理想治疗目标。