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原发性高血压患者β1肾上腺素能受体基因多态性与β1肾上腺素能受体阻滞剂反应

Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension.

作者信息

Karlsson J, Lind L, Hallberg P, Michaëlsson K, Kurland L, Kahan T, Malmqvist K, Ohman K P, Nyström F, Melhus H

机构信息

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

出版信息

Clin Cardiol. 2004 Jun;27(6):347-50. doi: 10.1002/clc.4960270610.

Abstract

BACKGROUND

Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the beta1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo.

HYPOTHESIS

The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the beta1-adrenergic receptor blocker atenolol.

METHODS

Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the beta1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism.

RESULTS

We found no significant associations between the changes in the measured variables and either of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency toward a greater reduction in heart rate compared with patients with the Ser/Ser49 genotype (p = 0.06).

CONCLUSIONS

The Ser49Gly and Arg389Gly beta1-adrenergic receptor polymorphisms do not seem to exert a major effect on the changes in heart rate and blood pressure during 12 weeks of treatment with atenolol in patients with essential hypertension and LV hypertrophy.

摘要

背景

研究表明,β1-肾上腺素能受体中的Ser49Gly和Arg389Gly多态性可能对心血管系统具有功能重要性。两者在体外均与受体活性改变相关,在体内与高血压和心力衰竭相关。

假设

本研究的目的是测试这些多态性是否与原发性高血压和左心室(LV)肥厚患者在使用β1-肾上腺素能受体阻滞剂阿替洛尔治疗期间心率或血压的变化相关。

方法

对101例经超声心动图证实有LV肥厚的高血压患者测量血压和心率,在一项双盲研究中随机分为接受β1-肾上腺素能受体阻滞剂阿替洛尔或血管紧张素II 1型受体拮抗剂厄贝沙坦治疗。12周后评估血压和心率的变化。使用聚合酶链反应和限制性片段长度多态性进行β1-肾上腺素能受体基因分型。

结果

我们发现测量变量的变化与两种多态性中的任何一种之间均无显著关联。然而,与Ser/Ser49基因型患者相比,49Gly等位基因携带者的心率降低趋势更大(p = 0.06)。

结论

在原发性高血压和LV肥厚患者中,使用阿替洛尔治疗12周期间,Ser49Gly和Arg389Glyβ1-肾上腺素能受体多态性似乎对心率和血压的变化没有主要影响。

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