Eadon Michael T, Chapman Arlene B
Division of Nephrology and Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; and Section of Nephrology, University of Chicago, Chicago, IL.
Division of Nephrology and Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; and Section of Nephrology, University of Chicago, Chicago, IL.
Adv Chronic Kidney Dis. 2016 Mar;23(2):91-105. doi: 10.1053/j.ackd.2016.02.003.
Hypertension is a multifactorial condition with diverse physiological systems contributing to its pathogenesis. Individuals exhibit significant variation in their response to antihypertensive agents. Traditional markers, such as age, gender, diet, plasma renin level, and ethnicity, aid in drug selection. However, this review explores the contribution of genetics to facilitate antihypertensive agent selection and predict treatment efficacy. The findings, reproducibility, and limitations of published studies are examined, with emphasis placed on candidate genetic variants affecting drug metabolism, the renin-angiotensin system, adrenergic signalling, and renal sodium reabsorption. Single-nucleotide polymorphisms identified and replicated in unbiased genome-wide association studies of hypertension treatment are reviewed to illustrate the evolving understanding of the disease's complex and polygenic pathophysiology. Implementation efforts at academic centers seek to overcome barriers to the broad adoption of pharmacogenomics in the treatment of hypertension. The level of evidence required to support the implementation of pharmacogenomics in clinical practice is considered.
高血压是一种多因素疾病，多种生理系统参与其发病机制。个体对抗高血压药物的反应存在显著差异。传统指标，如年龄、性别、饮食、血浆肾素水平和种族，有助于药物选择。然而，本综述探讨遗传学在促进抗高血压药物选择和预测治疗效果方面的作用。研究已发表研究的结果、可重复性和局限性，重点关注影响药物代谢、肾素-血管紧张素系统、肾上腺素能信号传导和肾脏钠重吸收的候选基因变异。对在高血压治疗的无偏全基因组关联研究中鉴定和重复的单核苷酸多态性进行综述，以说明对该疾病复杂多基因病理生理学的不断演变的理解。学术中心的实施工作旨在克服在高血压治疗中广泛采用药物基因组学的障碍。考虑了支持在临床实践中实施药物基因组学所需的证据水平。
