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Genetic factors in the pathogenesis of hypertension

Georg B Ehret, MD
Section Editors
George L Bakris, MD
Norman M Kaplan, MD
Deputy Editor
John P Forman, MD, MSc


Blood pressure is a classic quantitative genetic trait, and therefore, primary hypertension (formerly called "essential" hypertension) is of interest to clinicians and geneticists alike [1,2]. Family and twin studies estimate that the heritability of blood pressure is 30 to 50 percent [3-5]; consequently, genomics has the potential to contribute to the poorly understood pathogenesis of primary hypertension. Strong empirical evidence of the importance of genes in hypertension comes from the observation that hypertension is 2.4 times more common in subjects who have two hypertensive parents [6].

The genetic contribution to blood pressure regulation is of two fundamentally different types:

Monogenic hypertension and rare genetic variants – Rare mutations segregating in families can cause secondary hypertension, even in the absence of other risk factors (ie, "monogenic" hypertension, such as Liddle's syndrome) (table 1) (see "Genetic disorders of the collecting tubule sodium channel: Liddle's syndrome and pseudohypoaldosteronism type 1"). Once a monogenic form of hypertension is identified, these cases should be correctly labeled as secondary rather than primary hypertension. In addition to rare variants that are associated with secondary hypertension, there are rare mutations that lower blood pressure and therefore protect against the development of hypertension. One example is Gitelman syndrome in which loss-of-function mutations in the thiazide-sensitive Na-Cl cotransporter in the distal tubule are associated with lower blood pressures than in individuals without this defect (see "Bartter and Gitelman syndromes"). These monogenic hypotension syndromes are not further discussed in this topic.

Primary hypertension and common genetic variants – There are at least hundreds, possibly thousands, of common genetic hypertension risk variants that are individually associated with small effect sizes (approximately 1 mmHg or less). The probability of primary hypertension occurring grows larger with the number of risk alleles present and is modulated by environmental factors such as age, body mass index (BMI), sex, salt consumption, and others. Consequently, primary hypertension cannot be due to one or only a few genetic variants, and there is no such thing as the primary hypertension gene.

Patterns illuminated by the two different types of genetic contributions are distinctly different, and this topic will review both types of genetic variation.

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Literature review current through: Oct 2017. | This topic last updated: Feb 22, 2016.
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