Clinica dell'Ipertensione Arteriosa, Department of Medicine (DIMED), University of Padua, Via Giustiniani 2, 35126 Padua, Italy.
Nat Rev Endocrinol. 2017 May;13(5):289-298. doi: 10.1038/nrendo.2016.196. Epub 2017 Jan 6.
Studies involving adoptive families and twins have demonstrated the genetic basis of hypertension and shown that genetic factors account for about 40% of the variance in blood pressure among individuals. Arterial hypertension is genetically complex: multiple genes influence the blood pressure phenotype through allelic effects from single genes and gene-gene interactions. Moreover, environmental factors also modify the blood pressure phenotype. This complexity explains why the identification of the underlying genes has not been as successful in hypertension as in other diseases (such as type 1 and type 2 diabetes mellitus). The identification of the genetic determinants of hypertension has been most successful in endocrine forms of hypertension, which have well-defined phenotypes that permit a precise patient stratification into homogeneous cohorts. A promising area for the application of genetic testing to personalized medicine is the prediction of responses and adverse reactions to antihypertensive drugs. The identification of genetic markers of drug response will enable the design of randomized controlled trials in much smaller series of patients than is currently possible, decreasing the costs and times from drug design to clinical use and ultimately providing patients and doctors with a larger number of tools to combat hypertension, the most important risk factor for cardiovascular disease. This Review focuses on the rapidly developing field of genetic testing in patients with arterial hypertension.
研究表明,高血压具有遗传基础,且遗传因素大约可解释个体间血压 40%的变异。动脉高血压的遗传机制复杂,多个基因通过单基因的等位基因效应及基因-基因相互作用影响血压表型。此外,环境因素也可修饰血压表型。这一复杂性解释了为什么高血压的相关基因识别不如其他疾病(如 1 型和 2 型糖尿病)那样成功。在具有明确表型的内分泌型高血压中,高血压遗传决定因素的识别最为成功,这使得能够精确地将患者分层为同质队列。遗传检测在个体化医疗中的一个有前景的应用领域是预测抗高血压药物的反应和不良反应。药物反应的遗传标志物的鉴定将能够在比目前可能的更小的患者系列中设计随机对照试验,降低从药物设计到临床应用的成本和时间,最终为患者和医生提供更多的工具来对抗高血压,这是心血管疾病最重要的危险因素。本文综述了动脉高血压患者基因检测这一日益发展的领域。