Padmanabhan, S. and Joe, B. (2017) Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans. Physiological Reviews, 97(4), pp. 1469-1528. (doi: 10.1152/physrev.00035.2016) (PMID:28931564) (PMCID:PMC6347103)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Padmanabhan, Professor Sandosh |
| Authors: | Padmanabhan, S., and Joe, B. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Physiological Reviews |
| Publisher: | American Physiological Society |
| ISSN: | 0031-9333 |
| ISSN (Online): | 1522-1210 |
| Published Online: | 20 September 2017 |
| Copyright Holders: | Copyright © 2017 American Physiological Society |
| First Published: | First published in Physiological Reviews 97(4):1469-1528 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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