Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China.
Chin Med J (Engl). 2010 Jun;123(11):1382-6.
Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in beta1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I)/deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients.
Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.
The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P = 0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.
The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.
遗传因素可能影响美托洛尔的降压反应，许多研究集中在β1-肾上腺素能受体基因型与血压（BP）之间的关系上，而关于血管紧张素转换酶（ACE）基因型与美托洛尔治疗效果的关联知之甚少。本研究旨在探讨 ACE 基因插入（I）/缺失（D）多态性是否与中国汉族高血压患者对美托洛尔的反应有关。
96 例原发性高血压患者接受美托洛尔（100mg 每日一次）单药治疗 8 周。治疗前后进行 24 小时动态血压监测和动态心电图检查。采用 PCR 进行基因分型分析。观察 8 周治疗后 ACE 基因 I/D 多态性与 BP 和心率（HR）变化的关系。
ACE 基因 II 型患者 24 小时平均 HR 下降幅度大于 ID 或 DD 型患者（P=0.045），该基因型对坐姿 HR 或 BP 下降无影响。在校正年龄、性别、体重指数、BP 和基线 HR 后，ACE 基因 I/D 多态性仍是 24 小时平均 HR 变化的独立预测因子。
ACE 基因 II 多态性可能是中国汉族高血压患者接受美托洛尔治疗后 24 小时平均 HR 下降幅度更大的候选预测因子。II 型多态性患者从美托洛尔治疗中获益更大。需要更大的研究来验证这一发现。
