Universiteit Utrecht, Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Pharmacotherapy, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht, The Netherlands.
Expert Opin Drug Metab Toxicol. 2010 Apr;6(4):439-60. doi: 10.1517/17425250903571670.
Only 23 - 41% of hypertensive patients receiving antihypertensive drugs achieve adequate blood pressure control. Multiple physiological systems regulate blood pressure and variation in genes involved in these systems may account for enhanced or diminished blood pressure lowering response to antihypertensive therapy.
We explored explanations for variation in blood pressure response to antihypertensive drugs by linking genetic polymorphisms in renin-angiotensin-aldosterone system (RAAS) genes to antihypertensive drug response on intermediate parameters (e.g., potassium excretion, aldosterone levels). A MEDLINE search (1966 - 2008) was performed to identify publications reporting effects of genetic polymorphisms in the RAAS on antihypertensive drug response with regard to intermediate parameters.
With regard to the ACE insertion/deletion and the angiotensinogen -217G/A polymorphism variation in blood pressure response could be explained by effects on intermediate parameters. However, most studies that were identified with our search varied in study design, population and outcome, which complicate adequate comparisons.
Little evidence is available that explains these pharmacogenetic interactions. In the future, a better understanding of these mechanisms should provide a more solid evidence base for the individualized hypertension treatment based on genetic variation.
只有 23-41%的高血压患者接受抗高血压药物达到足够的血压控制。多种生理系统调节血压和基因变异在这些系统中可能会导致增强或减弱降压反应的抗高血压治疗。
我们探讨了通过链接肾素-血管紧张素-醛固酮系统(RAAS)基因的遗传多态性的解释血压对降压药物的反应,以抗高血压药物对中间参数(如,钾排泄,醛固酮水平)的反应。一个 MEDLINE 搜索(1966-2008)进行了鉴定报告影响遗传多态性 RAAS 对中间参数的抗高血压药物的反应。
关于 ACE 插入/缺失和血管紧张素原-217G/A 多态性变异血压反应可以通过对中间参数的影响来解释。然而,大多数研究中发现我们的搜索不同的研究设计,人群和结果,这使适当的比较复杂化。
很少有证据表明这些药物遗传学相互作用。在未来,更好地了解这些机制应提供一个更坚实的证据基础,为基于遗传变异的个体化高血压治疗。