GNB3基因C825T多态性与美托洛尔药效的相关性研究

Genetic polymorphism of GNB3 C825T in association with efficacy of metoptolol

目的:探讨G蛋白β3亚单位(G protein beta3 subunit,GNB3)基因多态性与原发性高血压患者服用美托洛尔治疗后血压变化的关系。方法:选择轻-中度原发性高血压患者97例,给予单剂美托洛尔缓释片,治疗8周,并采集患者血液标本。检测治疗前后血压、动态血压等。采用聚合酶链式反应-限制性片段长度多态性分析法(PCR-RFLP)对GNB3 C825T基因单核苷酸多态性(single nucleotide polymorphism,SNP)位点进行分型。数据采用方差分析方法,分析不同基因型患者服用美托洛尔降压疗效的差异,并采用stepwise线性回归方法分析可能预测美托洛尔治疗后血压水平的因素。结果:服用美托洛尔治疗后患者的血压、心率较治疗前明显下降(P<0.01)。GNB3 C825T基因多态性与美托洛尔治疗后夜间收缩压及舒张压下降有关,其中CC型下降最多:(11.1±9.3)mmHg/(7.9±5.8)mmHg,CT型次之:(5.8±12.9)mmHg/(4.5±8.6)mmHg,TT型最小:(3.6±13.7)mmHg/(3.0±7.9)mmHg,不同基因型患者之间比较具有统计学差异(P<0.05)。Stepwise多元回归分析结果进一步证实此相关性。结论:GNB3 C825T基因多态性与美托洛尔治疗后夜间收缩压及舒张压下降具有相关性。

Objective：To investigate the association of the polymorphism of GNB3 C825T with changes in blood pressure after metoprolol treatment in hypertensive patients.Methods：The hypertensive patients were treated with metoprolol for 8 weeks.The clinical measurements of baseline and after treatment included blood pressure and ambulatory blood pressure.The polymerase chain reaction-restriction fragment length polumorphism（PCR-RFLP） was used to detect the single nucleotide polymorphism（SNP） of GNB3 gene.The ANOVA and stepwise multiple regression analysis were used to assess whether gene polymorphisms are associated with cardiovascular response to metoprolol.Results：Metoprolol produced a significant decrease in the parameters of blood pressure and heart rate（P0.01）.GNB3 C825T genotype was associated with the decreases in nocturnal systolic blood pressure（SBP） and diastolic blood pressure（DBP）：CC：（11.1±9.3） mmHg/（7.9±5.8） mmHg;CT：（5.8±12.9） mmHg/（4.5±8.6） mmHg;TT：（3.6±13.7） mmHg/（3.0±7.9） mmHg.The falls were significantly different between the genotypes（CCCTTT,P0.05）,which was further confirmed by stepwise multiple regression analysis.Conclusion：GNB3 C825T polymorphism is associated with the decrease in nocturnal blood pressure response to metoprolol.