Fontana V, Luizon M R, Sandrim V C
Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas (Unicamp), Campinas, SP, Brazil.
Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
J Hum Hypertens. 2015 May;29(5):283-91. doi: 10.1038/jhh.2014.76. Epub 2014 Aug 28.
Hypertension is a leading cause of cardiovascular mortality, but only one third of patients achieve blood pressure goals despite antihypertensive therapy. Genetic polymorphisms may partially account for the interindividual variability and abnormal response to antihypertensive drugs. Candidate gene and genome-wide approaches have identified common genetic variants associated with response to antihypertensive drugs. However, there is no currently available pharmacogenetic test to guide hypertension treatment in clinical practice. In this review, we aimed to summarize the recent findings on pharmacogenetics of the most commonly used antihypertensive drugs in clinical practice, including diuretics, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, beta-blockers and calcium channel blockers. Notably, only a small percentage of the genetic variability on response to antihypertensive drugs has been explained, and the vast majority of the genetic variants associated with antihypertensives efficacy and toxicity remains to be identified. Despite some genetic variants with evidence of association with the variable response related to these most commonly used antihypertensive drug classes, further replication is needed to confirm these associations in different populations. Further studies on epigenetics and regulatory pathways involved in the responsiveness to antihypertensive drugs might provide a deeper understanding of the physiology of hypertension, which may favor the identification of new targets for hypertension treatment and genetic predictors of antihypertensive response.
高血压是心血管疾病死亡的主要原因，但尽管进行了抗高血压治疗，仍只有三分之一的患者达到血压目标。基因多态性可能部分解释个体间的变异性以及对抗高血压药物的异常反应。候选基因和全基因组方法已经确定了与抗高血压药物反应相关的常见基因变异。然而，目前尚无可用的药物遗传学检测方法来指导临床实践中的高血压治疗。在本综述中，我们旨在总结临床实践中最常用的抗高血压药物的药物遗传学最新研究结果，包括利尿剂、血管紧张素转换酶抑制剂、血管紧张素II受体阻滞剂、β受体阻滞剂和钙通道阻滞剂。值得注意的是，抗高血压药物反应的基因变异性仅得到了一小部分解释，与抗高血压药物疗效和毒性相关的绝大多数基因变异仍有待确定。尽管有一些基因变异与这些最常用抗高血压药物类别的可变反应存在关联证据，但仍需要在不同人群中进一步重复验证这些关联。对抗高血压药物反应所涉及的表观遗传学和调控途径的进一步研究可能会更深入地了解高血压的生理学，这可能有助于确定高血压治疗的新靶点和抗高血压反应的基因预测指标。
