目的 探讨G蛋白β3亚单位C825T基因多态性与富马酸比索洛尔降压疗效的相关性。方法 选择2018-10至2020-10在解放军总医院第一医学中心心内科住院或门诊就诊的轻、中度原发性高血压患者,均口服5 mg/d比索洛尔,进行GNβ3-C825T基因型测定,依据基因型分为3组:CC组、CT组、TT组,每组150例,在3组受试者治疗7 d,1、3、6个月后进行随访,测定患者的富马酸比索洛尔药物代谢血药浓度;治疗前、治疗7 d,1、3、6个月后进行24 h动态血压监测,比较患者静息状态下收缩压及舒张压(SBP、DBP),24 h收缩压均数(24 h SBP)、24 h舒张压均数(24 h DBP)、白天收缩压均数(d SBP)、白天舒张压均数(d DBP)、夜间收缩压均数(n SBP)、夜间舒张压均数(n DBP)的组间差异;进行24 h动态心电图监测,比较24 h平均心率、窦性心律震荡水平。结果 治疗7 d,随访1、3、6个月TT组富马酸比索洛尔血药浓度均高于CC组及CT组,差异均有统计学意义(P＜0.05),CC组与CT组无统计学差异,3组组内不同时间血药浓度变化均无统计学差异;应用富马酸比索洛尔后,3组患者血压均有下降趋势,其中TT组降压效果＞CT组＞CC组,3组间血压下降水平有统计学差异(P＜0.05);治疗7 d后,动态心电图显示:3组患者心率有下降趋势,TT组＞CT组＞CC组,其中TT组与CT组、CC组比较有统计学差异(P＜0.05),CT组与CC组心率下降无统计学差异;TT组窦性心律震荡水平优于CT组、CC组。结论 G蛋白β3亚单位C825T基因多态性与富马酸比索洛尔降压疗效之间具有相关性。
Abstract
Objective To study the correlations between Gnβ3-C825T gene polymorphism and the antihypertensive effect of bisoprolol fumarate.Methods Inpatients and outpatients with low-grade and moderate-grade hypertension treated in the First Medical Center received 5 mg/d bisoprolol orally. Their Gnβ3-C825T genotypes were detected, According to genotypes, these patients were divided into three groups: CC type, CT type and TT type groups, with 150 participants in each group. They were followed up 7 days, 1, 3 and 6 months after treatment.The blood concentration of bisoprolol fumarate was measured.24-hour dynamic blood pressure was recorded, and systolic blood pressure and diastolic blood pressure (SBP and DBP) under resting state were compared.24 h mean systolic blood pressure (24 h SBP), 24 h mean diastolic blood pressure (24 h DBP), daytime mean systolic blood pressure (D SBP), daytime mean diastolic blood pressure (D DBP), night mean systolic blood pressure (N SBP) and night mean diastolic blood pressure (N DBP) were compared between these groups.24-hour dynamic electrocardiograms were recorded to compare the 24-hour average heart rate and the heart rate turbulence (HRT) level.Results The blood concentration of bisoprolol fumarate in the TT group was higher than in the other two groups, and the difference was statistically significant (P< 0.05), but there was no statistically significant difference between the CC group and CT group. There was no significant difference in blood concentration between these patients 1, 3 and 6 months after treatment. After the application of bisoprolol fumarate, blood pressure of the three groups trended down, and the antihypertensive effect was the best in the TT group, followed by the CT group and CC group, and there was statistically significant difference in blood pressure reduction between the three groups (P<0.05). After 7 days of treatment, dynamic electrocardiograms showed that the heart rate of the three groups began to decrease, and there was statistically significant difference between the TT group and the other two groups, but not between the CT group and the CC group. The level of heart rate turbulence (HRT) in the TT group is better than in the other two groups.Conclusions The polymorphism of Gnβ3-C825T genes is correlated with the antihypertensive efficacy of bisoprolol fumarate.
关键词
G蛋白β3亚单位C825T基因 /
高血压 /
富马酸比索洛尔
Key words
Gnβ3-C825T gene /
high blood pressure /
bisoprolol fumarate
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基金
心馨-默克心血管基金(2017A0002)。
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