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Genetic Basis of Salt-Sensitive Hypertension in Humans

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Genes and Cardiovascular Function

Abstract

The genetic network responsible for blood pressure (BP) variation in the general population and specifically the hypertensive population remains elusive. Several recent genome-wide association studies (GWAS) have identified and confirmed loci associated with BP and hypertension. However, only a small fraction of the trait is currently explained. This apparent deficit relative to the estimates for heritability can be due to several factors, a major one being the poor assessment of the phenotype, i.e. BP. All GWAS have used so far office BPs, which are notoriously variable. Imputation of BP in treated subjects is done by a fixed number. In addition, BPs are usually being “adjusted” for e.g. age, gender or body mass index under the assumption that these do not alter BP systematically by genotype, an assumption that appears no longer valid.

A better approach may include more specific assessment of the actual BP level in a given individual for both cases and controls, preferably by 24-h ambulatory BP monitoring, for cases off antihypertensive therapy, and to stratify for factors such as sex, age and body mass index. This approach will likely provide better insight into the distinct genetic architectures contributing to different hypertension phenotypes and explain a substantially larger part of the BP variance. Further improvements will likely emerge when other environmental/lifestyle factors are incorporated, such as extent of alcohol intake, stress, salt intake or physical activity. In the ongoing Ottawa GWAS for BP response to salt, we hope to identify loci and genes associated with salt-sensitive versus salt-resistant hypertension.

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Acknowledgments

The authors would like to acknowledge Mrs. Danielle Oja for her excellent skills in assisting in the preparation and formatting of the chapter.

The authors’ research discussed in this chapter is being supported by operating grants from the Canadian Institutes of Health Research.

Frans H. H. Leenen is supported by the Pfizer Chair in Hypertension Research, an Endowed Chair supported by Pfizer Canada, University of Ottawa Heart Institute Foundation and the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. University of Ottawa Heart Institute, Ottawa, ON, Canada

    Frans H. H. Leenen, Md. Shahrier Amin & Alexandre F. R. Stewart

  2. Health Sciences, Ottawa, ON, Canada

    Frederique Tesson

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  1. Frans H. H. Leenen
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  2. Md. Shahrier Amin
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  3. Alexandre F. R. Stewart
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  4. Frederique Tesson
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Correspondence to Frans H. H. Leenen .

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  1. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Leenen, F.H.H., Amin, S., Stewart, A.F.R., Tesson, F. (2011). Genetic Basis of Salt-Sensitive Hypertension in Humans. In: Ostadal, B., Nagano, M., Dhalla, N. (eds) Genes and Cardiovascular Function. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7207-1_16

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