β1肾上腺素能受体基因多态性及其甲基化修饰对美托洛尔降压疗效的影响

Influence on Metoprolol Antihypertensive Effect of β1-Adrenoreceptor Gene Polymorphism and its Methylation

目的研究β1肾上腺素能受体基因多态性及其甲基化修饰对美托洛尔降压疗效的影响。方法入选300例高血压病患者,给予相同剂量美托洛尔降压治疗,同时用聚合酶链反应限制片长多态性法检测其基因型,比较不同基因型高血压患者血压下降水平;用甲基化特异性聚合酶链反应法检测相同基因型高血压患者和正常血压者β1肾上腺素能受体基因甲基化修饰情况。结果美托洛尔治疗后,Arg389Arg型患者舒张压较Gly389Arg型和Gly389Gly型患者明显下降(降幅8.0%±1.3%比4.0%±1.5%和3.0%±1.1%,P<0.05);三种基因型患者收缩压下降幅度差异无显著性。所有研究对象外周血中β1肾上腺素能受体基因均存在甲基化修饰。结论β1肾上腺素能受体的Gly389Arg基因多态性与美托洛尔降压疗效相关;外周血β1肾上腺素能受体基因甲基化修饰未发现与美托洛尔降压疗效相关。

Aim To investigate whether antihypertensive efficacy in patients with hyprtension was impacted by polymorphism and methylafion β1-adrenoreceptor （β1-AR） gone. Methods Three hundred hypertensive patients enrolled began taking metoprolol by the same dose; the genotype of their β1-AR gene by PCR-RFLP was tested to compare the anfihypertensive efficacy among patients with different genotype. The methylation state in β1-AR gene detected by methylation specific PCR （MSP） from peripheral blood of patients with the same genotype was controlled by the subjects with normal blood pressure, to make a inquiry into the relationship between the modification and the antihypertensive response to metoprolol. Results Patients with Arg389Arg genotype got significant greater decrease in diastolic blood pressure as compared with Gly389Arg and Gly389Gly （8. 0% ± 1.3% vs 4.0% ± 1.5% and 3.0% ± 1.1%, P 〈 0.05 ） ; and the β1-AR gene from peripheral blood of all subjects was methylated. Conclusions Polymorphism at Gly389Arg of β1-AR gene was associated with antihypertensive response to metoprolol; the methylated modification on β1-AR gone from human peripheral blood was not found to be related to the response.