Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans

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)

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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 > Institute of Cardiovascular and Medical Sciences
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
676621Ancestry and biological informative markers for stratification of hypertension - The AIM HY studySandosh PadmanabhanMedical Research Council (MRC)MR/M016560/1RI CARDIOVASCULAR & MEDICAL SCIENCES
570081Genetic, molecular and functional dissection of a novel pathway for hypertension: Uromodulin, renal function, sodium homeostasis and blood pressure.Sandosh PadmanabhanBritish Heart Foundation (BHF)PG/12/85/29925RI CARDIOVASCULAR & MEDICAL SCIENCES
689911Clinical study of UMOD NKCC2 interaction on salt-sensitivity in hypertensionSandosh PadmanabhanBritish Heart Foundation (BHF)CS/16/1/31878RI CARDIOVASCULAR & MEDICAL SCIENCES