Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Geneva, Switzerland.
Eur Heart J. 2013 Apr;34(13):951-61. doi: 10.1093/eurheartj/ehs455. Epub 2013 Jan 9.
Hypertension (HTN) is quantitatively the major cardiovascular risk factor and responsible for ∼50% of cardiovascular morbidity and mortality. Blood pressure (BP) is also a classical complex genetic trait with heritability estimates of 30-50%. Although much is known about BP regulation, the intrinsic origin of essential HTN remains obscure although many environmental factors are known. Analyses of rare monogenic syndromes of HTN have focused attention on pathways that involve renal sodium handling, and steroid hormone metabolism including the mineralocorticoid receptor activity. The genetic basis of common essential HTN on the other hand is only just becoming accessible through high-throughput approaches. Unbiased genome-wide analyses of BP genomics have identified 43 genetic variants associated with systolic, diastolic BP, and HTN. It is highly likely based on current findings that there are hundreds of such loci with small effects on BP, opening a perspective on the genetic architecture of BP that was unknown before. It is our hope that the knowledge of these and further loci will lead to improved understanding of BP pathophysiology and to the identification of new targets for drug therapy.
高血压(HTN)是心血管疾病的主要风险因素,其导致的心血管发病率和死亡率约占 50%。血压(BP)也是一种经典的复杂遗传特征,其遗传度估计为 30-50%。尽管人们对血压调节有了很多了解,但原发性高血压的内在起源仍然不清楚,尽管已经知道许多环境因素。对高血压的罕见单基因综合征的分析集中在涉及肾脏钠处理和类固醇激素代谢的途径上,包括醛固酮受体活性。另一方面,常见的原发性高血压的遗传基础仅通过高通量方法才刚刚开始被揭示。对血压基因组学的无偏基因组分析已经确定了 43 个与收缩压、舒张压和高血压相关的遗传变异。根据目前的发现,很可能有数百个这样的对血压有微小影响的位点,这为以前未知的血压遗传结构提供了一个视角。我们希望这些和其他位点的知识将有助于更好地理解血压的病理生理学,并确定新的药物治疗靶点。