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Gonzalez-Jaramillo, V.* ; Portilla-Fernandez, E.* ; Glisic, M.* ; Voortman, T.* ; Bramer, W.* ; Chowdhury, R.* ; Roks, A.J.M.* ; Jan Danser, A.H.* ; Muka, T.* ; Nano, J. ; Franco, O.H.*

The role of DNA methylation and histone modifications in blood pressure: A systematic review.

J. Hum. Hypertens. 33, 703-715 (2019)
Postprint DOI PMC
Open Access Green
Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to systematically review studies investigating the association between epigenetic marks (global, candidate-gene or genome-wide methylation of DNA, and histone modifications) and blood pressure or hypertension. Five bibliographic databases were searched until the 7th of December 2018. Of 2984 identified references, 26 articles based on 25 unique studies met our inclusion criteria, which involved a total of 28,382 participants. The five studies that assessed global DNA methylation generally found lower methylation levels with higher systolic blood pressure, diastolic blood pressure, and/or presence of hypertension. Eighteen candidate-gene studies reported, in total, 16 differentially methylated genes, including renin-angiotensin-system-related genes (ACE promoter and AGTR1) and genes involved in sodium homeostasis and extracellular fluid volume maintenance system (NET promoter, SCNN1A, and ADD1). Between the three identified epigenome-wide association studies (EWAS), lower methylation levels of SULF1, EHMT2, and SKOR2 were found in hypertensive patients as compared with normotensive subjects, and lower methylation levels of PHGDH, SLC7A11, and TSPAN2 were associated with higher systolic and diastolic blood pressure. In summary, the most convincing evidence has been reported from candidate-gene studies, which show reproducible epigenetic changes in the interconnected renin-angiotensin and inflammatory systems. Our study highlights gaps in the literature on the role of histone modifications in blood pressure and the need to conduct high-quality studies, in particular, hypothesis-generating studies that may help to elucidate new molecular mechanisms.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Genome-wide Association; 11-beta-hydroxysteroid Dehydrogenase Type-2; Essential-hypertension; Promoter Methylation; Angiotensin-ii; Heart-disease; Gene-body; Risk; Loci; Hypomethylation
ISSN (print) / ISBN 0950-9240
e-ISSN 1476-5527
Journal Journal of Human Hypertension
Quellenangaben Volume: 33, Issue: 10, Pages: 703-715 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)