Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the “structural backbone,” this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex “triad” of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach.

中文翻译：

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迈向高血压的精准医学：对实验大鼠模型和人类血压的基因组、表观基因组和微生物组学影响的回顾

原发性高血压的遗传性质令人信服的证据导致了对大鼠和人类的广泛研究。大鼠已成为研究高血压遗传学的主要模型，从而确定了与高血压有因果关系的基因组区域。最近，人类全基因组研究也开始提高我们对多基因高血压遗传的理解。基于以高血压遗传学为“结构骨干”的研究的时间顺序，本综述对大鼠和人类遗传元素进行了分类和讨论，这些遗传元素在血压调节中具有重要意义。此外，从这些遗传研究中获得的知识提供了证据，表明遗传对高血压的影响存在于我们 DNA 的非编码元件中，并通过普遍的上位性或基因-基因相互作用发挥作用。最后，记录了当前认为基因组、表观基因组和微生物组的更复杂“三元组”影响高血压遗传的观点。总体而言，从大鼠和人类获得的集体知识令人失望，因为作为原发性高血压临床管理目标的主要高血压基因可能不是临床现实。另一方面，