β1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol
β1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol
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DOI：
10.1016/s0009-9236(03)00068-7
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发表时间：
2003-07-01
影响因子：
6.7
通讯作者：
Pauly, DF
中科院分区：
文献类型：
--
作者：
Johnson, JA;Zineh, I;Pauly, DF
目的：β受体阻滞剂单药治疗的血压反应存在显著的患者间差异。我们测试的假设，2个常见的多态性基因β（1）-肾上腺素能受体与美托洛尔的降压反应与患者无并发症hypertension.Methods：40高血压男性和女性，年龄35至65岁。基线研究包括24小时动态血压监测。患者服用美托洛尔50 mg，每日两次，每周滴定至反应或200 mg，每日两次。以稳定剂量给药至少4周后，重复进行治疗期24小时动态血压监测。采用聚合酶链反应-限制性片段长度多态性技术检测β 1肾上腺素能受体49和389密码子基因型。进行多元线性回归以确定基因型和其他变量对血压对美托洛尔的反应的影响。结果：与携带变异等位基因的患者相比，密码子389为Arg纯合子的患者日间舒张压降低近3倍（-13.3% +/- 8.4% vs-4.5% +/-8.2%，P = 0.0018）。β（1）-肾上腺素能受体的单倍型对（双倍型）也是反应的重要预测因子，具有Ser 49 Arg 389/Ser 49 Arg 389双倍型的患者显示血压下降14.7 mm Hg，而具有G1 y 49 Arg 389/Ser 49 Gly 389双倍型的患者显示血压下降0.5 mm Hg。在多元回归分析中，基线日间舒张压，密码子389基因型，和密码子49基因型是显着的治疗后的血压predictor。结论：我们的数据表明，β（1）-肾上腺素能受体多态性是重要的决定因素，降压反应美托洛尔。将来，密码子49和389基因型或β（1）-肾上腺素能受体单倍型可能用于预测高血压患者对美托洛尔的舒张压反应。
Objectives: Marked interpatient variability exists in blood pressure response to beta-blocker monotherapy. We tested the hypothesis that 2 common polymorphisms in the gene for beta(1)-adrenergic receptor are associated with antihypertensive response to metoprolol in patients with uncomplicated hypertension.Methods: Forty hypertensive men and women aged 35 to 65 years were studied. Baseline studies included 24-hour ambulatory blood pressure monitoring. Patients took 50 mg metoprolol twice daily with weekly titration to response or 200 mg twice daily. After a minimum of 4 weeks at stable dose, treatment phase 24-hour ambulatory blood pressure monitoring was repeated. The codon 49 and 389 genotypes for beta(1)-adrenergic receptor were determined by polymerase chain reaction with restriction fragment length polymorphism. Multilinear regression was performed to determine the impact of genotype and other variables on blood pressure response to metoprolol.Results: Patients homozygous for Arg at codon 389 had a nearly 3-fold greater reduction in daytime diastolic blood pressure (-13.3% +/- 8.4% versus -4.5% +/- 8.2%, P =.0018) compared with those who carried the variant allele. The haplotype pair (diplotype) for beta(1)-adrenergic receptor was also a significant predictor of response, with patients having the Ser49Arg389/Ser49Arg389 diplotype demonstrating a decline in blood pressure of 14.7 mm Hg versus 0.5 mm Hg in patients with the G1y49Arg389/Ser49Gly389 diplotype. In multiregression analysis, baseline daytime diastolic blood pressure, codon 389 genotype, and codon 49 genotype were significant predictors of blood pressure after treatment.Conclusions: Our data suggest that beta(1)-adrenergic receptor polymorphisms are important determinants of antihypertensive response to metoprolol. In the future, codon 49 and 389 genotypes or beta(1)-adrenergic receptor haplotypes might be used to predict the diastolic blood pressure response to metoprolol in patients with hypertension.