Zateyshchikov Dmitry A, Minushkina Larissa O, Brovkin Alexey N, Savel'eva Ekaterina G, Zateyshchikova Anna A, Manchaeva Baira B, Nikitin Alexey G, Sidorenko Boris A, Nosikov Valery V
Scientific-Educational Medical Centre of General Management, Department of Russian President, Marshal Timoshenko str 21, Moscow, Russia.
Fundam Clin Pharmacol. 2007 Aug;21(4):437-43. doi: 10.1111/j.1472-8206.2007.00518.x.
Betaxolol is a selective antagonist of beta(1)-adrenergic receptors. Personal response to the drug widely varies and depends on its properties and individual features including innate characteristics. Our aim was to study the association between the clinical response to betaxolol in patients with essential hypertension (EH) and polymorphous markers of two genes: beta(1) adrenergic receptor gene (ADRB1) and cytochrome P450 2D6 gene (CYP2D6). Eighty-one patients with EH were selected. Mean age was 52.2 +/- 1.22 years. Betaxolol monotherapy provided effective blood pressure control (BP < 140/90 mmHg) in 68 patients, 56 of them continued treatment with initial dose. The systolic (SBP) and diastolic (DBP) blood pressure declined significantly at the end of the study. We have not found any significant association of rest and exercise BP and heart rate (HR) with polymorphous marker Arg389Gly of ADRB1 gene except the nighttime variability of DBP. But in case of the polymorphous marker Pro34Ser of CYP2D6 gene we have found significant association with response to betaxolol therapy. The rest HR declined more significantly in Ser/Pro genotype carriers (-32.6 +/- 4.77 beats/min and -18.4 +/- 2.01 beats/min, P = 0.023). These patients demonstrated more significant increase of exercise time (4.58 +/- 0.90 and 0.59 +/- 0.58 min, P = 0.045). Maximal exercise HR and DBP were also significantly lower in Ser/Pro genotype carriers in comparison with Ser/Ser genotype carriers. Decline of mean daytime SBP in 24-h ambulatory blood pressure monitoring was more significant in Pro allele carriers (-21.0 +/- 2.55 mmHg vs. -5.2 +/- 2.27 mmHg in patients with Ser/Ser genotype, P = 0.001). Betaxolol effect on HR and BP significantly depends on variability of the gene determining the drug metabolism. The carriers of Pro34 allele of CYP2D6 gene (8.6%) are more sensitive to betaxolol therapy. Because of the relatively small group sizes our data should be considered as preliminary ones. The increase of our groups and the replication in other studies will permit to estimate the contribution of genetic factors to betaxolol effect on HR and BP.
倍他洛尔是一种β1肾上腺素能受体的选择性拮抗剂。个体对该药物的反应差异很大，取决于其特性和个体特征，包括先天特征。我们的目的是研究原发性高血压（EH）患者对倍他洛尔的临床反应与两个基因的多态性标记之间的关联：β1肾上腺素能受体基因（ADRB1）和细胞色素P450 2D6基因（CYP2D6）。选取了81例EH患者。平均年龄为52.2±1.22岁。倍他洛尔单药治疗使68例患者的血压得到有效控制（血压<140/90 mmHg），其中56例继续使用初始剂量治疗。研究结束时，收缩压（SBP）和舒张压（DBP）显著下降。除了DBP的夜间变异性外，我们未发现静息和运动时的血压及心率（HR）与ADRB1基因的多态性标记Arg389Gly有任何显著关联。但对于CYP2D6基因的多态性标记Pro34Ser，我们发现其与对倍他洛尔治疗的反应有显著关联。Ser/Pro基因型携带者的静息心率下降更为显著（-32.6±4.77次/分钟和-18.4±2.01次/分钟，P = 0.023）。这些患者的运动时间增加更为显著（4.58±0.90和0.59±0.58分钟，P = 0.045）。与Ser/Ser基因型携带者相比，Ser/Pro基因型携带者的最大运动心率和DBP也显著更低。在24小时动态血压监测中，Pro等位基因携带者的日间平均SBP下降更为显著（-21.0±2.55 mmHg，而Ser/Ser基因型患者为-5.2±2.27 mmHg，P = 0.001）。倍他洛尔对心率和血压的影响显著取决于决定药物代谢的基因变异性。CYP2D6基因Pro34等位基因的携带者（8.6%）对倍他洛尔治疗更为敏感。由于样本量相对较小，我们的数据应被视为初步数据。增加我们的样本量并在其他研究中进行重复，将有助于评估遗传因素对倍他洛尔对心率和血压影响的贡献。
