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Genomics of Cardiovascular Measures of Autonomic Tone

Sigurdsson, Martin, I., MD, PhD*; Waldron, Nathan, H., MD, MHSc*; Bortsov, Andrey, V., MD, PhD; Smith, Shad, B., PhD; Maixner, William, DDS, PhD

Journal of Cardiovascular Pharmacology: March 2018 - Volume 71 - Issue 3 - p 180–191
doi: 10.1097/FJC.0000000000000559
Review Article
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Abstract: The autonomic nervous system exerts broad control over the involuntary functions of the human body through complex equilibrium between sympathetic and parasympathetic tone. Imbalance in this equilibrium is associated with a multitude of cardiovascular outcomes, including mortality. The cardiovascular static state of this equilibrium can be quantified using physiological parameters such as heart rate (HR), blood pressure, and by spectral analysis of HR variability. Here, we review the current state of knowledge of the genetic background of cardiovascular measurements of autonomic tone. For most parameters of autonomic tone, a large portion of variability is explained by genetic heritability. Many of the static parameters of autonomic tone have also been studied through candidate-gene approach, yielding some insight into how genotypes of adrenergic receptors affect variables such as HR. Genome-wide approaches in large cohorts similarly exist for static variables such as HR and blood pressure but less is known about the genetic background of the dynamic and more specific measurements, such as HR variability. Furthermore, because most autonomic measures are likely polygenic, pathway analyses and modeling of polygenic effects are critical. Future work will hopefully explain the control of autonomic tone and guide individualized therapeutic interventions.

*Division of Cardiothoracic Anesthesiology, Critical Care Medicine, Duke University Medical Center, Durham, NC; and

Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC.

Reprints: Martin I. Sigurdsson, MD, PhD, Department of Anesthesiology, Duke University Medical Center, DUMC 2094, 2301 Erwin Rd, Durham, NC 27710 (e-mail: martin.sigurdsson@duke.edu) or William Maixner, DDS, PhD, Genome Science Research Building (GSRB1/Snyderman), 905 S. LaSalle St, Durham, NC 27710 (e-mail: William.maixner@duke.edu).

Supported by the National Institutes of Health and the National Institute of Dental and Craniofacial Research (Grants U01-DE017018; W.M. and P01NS045685; W.M.). N. H. Waldron is supported by an American Heart Association Mentored Clinical and Population Research Award (16MCPRP30700010).

W. Maixner and S. B. Smith have equity ownership in Algynomics Inc. W. Maixner is a on a patent application related to COMT haplotypes and pain sensitivity, which has been licensed to Proove Biosciences. W. Maixner is also on the Board of Directors of Orthogen Inc. These relationships have been reviewed in conjunction with this research and are under management by the University of North Carolina at Chapel Hill and Duke University. The remaining authors report no conflicts of interest.

M. I. Sigurdsson and N. H. Waldron are equally contributed.

Received October 16, 2017

Accepted November 28, 2017

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