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

Journal of Human Hypertension volume 33, pages 703–715 (2019)Cite this article

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Abstract

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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  • 27 August 2019

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Acknowledgements

The contributions of the authors were as follows: VG, EP, and MG screened title/abstract. VG obtained full text, determined eligibility of articles, and participated in data extraction. VG and EP assessed the quality of the included studies. EP participated in data synthesis/analysis and interpretation of the data. VG, EP, and JN drafted the final paper. All authors contributed to the critical revision of the paper and approved the final version.

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Author notes

  1. These authors contributed equally: Valentina Gonzalez-Jaramillo, Eliana Portilla-Fernandez

  2. These authors jointly supervised this work: Jana Nano, Oscar H. Franco

Authors and Affiliations

  1. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands

    Valentina Gonzalez-Jaramillo, Eliana Portilla-Fernandez, Marija Glisic, Trudy Voortman, Taulant Muka, Jana Nano & Oscar H. Franco

  2. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland

    Valentina Gonzalez-Jaramillo, Taulant Muka & Oscar H. Franco

  3. Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands

    Eliana Portilla-Fernandez, Anton J. M. Roks & A. H. Jan Danser

  4. Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany

    Marija Glisic & Wichor Bramer

  5. Medical Library, Erasmus University Medical Center, Rotterdam, Netherlands

    Rajiv Chowdhury

  6. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Jana Nano

  7. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Jana Nano

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  1. Valentina Gonzalez-Jaramillo
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Gonzalez-Jaramillo, V., Portilla-Fernandez, E., Glisic, M. et al. The role of DNA methylation and histone modifications in blood pressure: a systematic review. J Hum Hypertens 33, 703–715 (2019). https://doi.org/10.1038/s41371-019-0218-7

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