Minushkina L O, Zateĭshchikova A A, Zateĭshchikov D A, Mankhaeva B B, Savel'eva E G, Kochkina M S, Brovkin A V, Nikitin A G, Nosikov V V, Sidorenko B A
Presidential Medical Center of Russia, Moscow, Russia.
Kardiologiia. 2008;48(3):20-6.
Association of polymorphism of b1-adrenoreceptors gene and cytochrome 2D6 gene with efficacy of b-adrenoblocker betaxolol was studied in 81 patients with I and II degree arterial hypertension. Betaxolol (10-20 mg/day) was given for 4 weeks, its efficacy was assessed by office blood pressure (BP) measurements, 24-hour BP and ECG monitoring and standard exercise test. At the end of the study significant lowering of systolic and diastolic BP was noted by 11,8 +/- 2,47 (p=0,001) and 7,8 +/- 1,68 mm Hg (p=0,001), respectively. Heart rate (HR) at rest lowered by 19,8 +/- 1,96 beats/min (p=0,0001). At analysis of individual reaction of patients to treatment with betaxolol it turned out that decrease of BP and HR was variable, but their distribution in the group did not differ significantly from normal. Hypotensive activity and influence on HR were confirmed by results of all instrumental investigations. No significant differences were revealed in dynamics of systolic and diastolic BP both at rest and at effort between patients with different genotypes of polymorphic marker Gly389Arg of ADRB1 gene. Compared with carriers of genotype Ser/Ser carriers of genotype Ser/Pro of polymorphic marker Pro34Ser of Cyp2D6 gene had significantly more pronounced decrease of HR at the background of treatment with betaxolol: - 32,6 +/- 4,77 and - 18,4 +/- 2,01 beats/min (p=0,023) at rest and - 30,1 +/- 3,05 and - 24,0 +/- 2,59 beats/min (p=0,043) at maximal exercise, respectively. These patients had also more pronounced lowering of diastolic BP at maximal work load and more pronounced increase of exercise duration at the background of treatment. Thus efficacy of betaxolol in patients with hypertension was associated solely with genotype of polymorphic marker Ser34Pro of CYP2D6 gene. In patients having in genotype Pro allele of polymorphic marker Pro34Ser of CYP2D6 gene therapy with betaxolol is more effective, than in homozygote carriers of Ser allele. This can be related to low rate of metabolism of the preparation in these patients.
在81例I级和II级高血压患者中研究了β1 - 肾上腺素能受体基因和细胞色素P450 2D6基因多态性与β - 肾上腺素能阻滞剂倍他洛尔疗效的关系。给予倍他洛尔（10 - 20mg/天）4周，通过诊室血压（BP）测量、24小时血压和心电图监测以及标准运动试验评估其疗效。研究结束时，收缩压和舒张压分别显著降低11.8±2.47（p = 0.001）和7.8±1.68mmHg（p = 0.001）。静息心率（HR）降低19.8±1.96次/分钟（p = 0.0001）。在分析患者对倍他洛尔治疗的个体反应时发现，血压和心率的降低是可变的，但它们在组内的分布与正常情况无显著差异。所有仪器检查结果均证实了倍他洛尔的降压活性及其对心率的影响。ADRB1基因多态性标记Gly389Arg不同基因型的患者在静息和运动时收缩压和舒张压的动态变化均无显著差异。与Cyp2D6基因多态性标记Pro34Ser基因型Ser/Ser携带者相比，Ser/Pro基因型携带者在倍他洛尔治疗背景下心率降低更为明显：静息时分别为 - 32.6±4.77和 - 18.4±2.01次/分钟（p = 0.023），最大运动时分别为 - 30.1±3.05和 - 24.0±2.59次/分钟（p = 0.043）。这些患者在最大工作负荷时舒张压降低也更明显，且在治疗背景下运动持续时间增加更明显。因此，倍他洛尔在高血压患者中的疗效仅与CYP2D6基因多态性标记Ser34Pro的基因型有关。在CYP2D6基因多态性标记Pro34Ser基因型为Pro等位基因的患者中，倍他洛尔治疗比Ser等位基因纯合子携带者更有效。这可能与这些患者中该制剂的低代谢率有关。
