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Pharmacogenomics of primary hypertension--the lessons from the past to look toward the future.

机译：原发性高血压的药物基因组学-从过去的教训中展望未来。

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摘要

A number of recent reviews have addressed the issue of the pharmacogenomics of primary hypertension and related complications by considering the data on the genotype-drug response relationship. Here we mainly discuss the methodological aspects of this issue, trying to integrate 'traditional' clinical and experimental pathophysiology and therapy-pharmacology with the 'new' genetics. Such integration is indispensable to: a). define the appropriate 'context' (genetic background, environment, age, gender, phase of hypertension, previous therapy etc.) in which a given genotype-drug response relationship should be tested (it is indeed likely that many discrepancies among published data originate from context's interference); b). assign the correct clinical meaning to the results obtained by statistics and functional genetics methodologies; c). define a novel clinical entity caused by a disease favoring allele, alone or in combination with other alleles, with a consistent clinical picture, prognosis and responsiveness to the appropriate drug; d). estimate the size of the population target amenable to benefit from a therapeutic intervention developed according to the pharmacogenomics' principles; e). develop a novel drug that selectively interferes with the sequence of events triggered by the genetic mechanism(s) underlying the clinical entity. Peculiar to this strategy is to look for consistency among findings gathered from different 'contexts' after having properly accounted for the context's dependency of the results.
机译：通过考虑有关基因型-药物反应关系的数据，许多近期的评论已经解决了原发性高血压和相关并发症的药物基因组学问题。在这里，我们主要讨论这个问题的方法论方面，试图将“传统的”临床和实验病理生理学以及治疗药理学与“新的”遗传学结合起来。这种集成对于以下内容必不可少：定义适当的“背景”（遗传背景，环境，年龄，性别，高血压阶段，以前的治疗方法等），应在其中测试给定的基因型-药物反应关系（确实有可能许多已发表数据之间的差异源自上下文的干扰）; b）。为通过统计学和功能遗传学方法获得的结果赋予正确的临床意义; C）。定义一种由有利于等位基因的疾病（单独或与其他等位基因组合）引起的新型临床实体，并具有一致的临床图像，预后和对适当药物的反应性; d）。估计可从根据药物基因组学原理开发的治疗干预措施中受益的目标人群的规模; e）。开发一种新药，该药选择性地干扰由临床实体潜在遗传机制触发的事件序列。该策略的特殊之处在于，在适当考虑了结果对上下文的依赖性之后，要在从不同“上下文”收集的发现之间寻找一致性。

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