Genetics of Hypertension – An Overview

  • A. G. Motulsky
  • W. Burke


Hypertension represents the upper range of the continuous distribution of blood pressure seen in human populations. High blood pressure is a multifactorial trait requiring both genetic and environmental factors for its manifestation. Genetic heterogeneity is likely. Certain underdeveloped populations have no hypertension but some individuals from such groups have the genetic make-up to develop high blood pressure when exposed to Western-style-environments. The specific genes involved in human hypertension are largely unknown. Genetic studies of blood pressure require attention to intermediate phenotypes with effects that are close to the mechanisms involved in blood pressure regulation. Ion exchange across cell membranes in kidney and/or smooth muscle cells may be involved, as shown by studies of red cell sodium-lithium countertransport (CT). A unique single gene appears to be responsible for elevated CT and may contribute as much as one-fifth of the attributable risk for systolic hypertension. Genetic animal models for hypertension may not reflect the genes operative in human hypertension.

Hypertension is a common trait with familial aggregation (see Ward 1990; Burke and Motulsky 1991, for extensive literature citations). Its genetic etiology appears to be heterogeneous. Rarely, a monogenic condition such as polycystic kidneys may be the cause of hypertension. The cut-off point of 140/90 mm to 160/90 mmHg to define high blood pressure is somewhat arbitrary and is selected to designate individuals at higher risk for renal and vascular complications. The distribution of blood pressure in populations approximates a Gaussian distribution. The shape of this curve explains why the majority of the 15 %–20 % of persons designated as hypertensives will have only mild or moderate hypertension. Hypertension by itself is not a disease but represents a risk factor for stroke, congestive heart failure, coronary heart disease, and renal failure. Not every person — even with severe hypertension — develops these medical complications. We do not know what factors determine which of these complications will develop in a given patient. Genetic factors might explain the predilection for a certain complication such as strokes among some families.

Using the diagnosis of hypertension by itself as a clinical entity is hazardous for genetic studies because of the heterogeneous etiology of high blood pressure. Findings that apply to one family may not apply to others and it is difficult to draw meaningful conclusions if the underlying biologic determinants vary between families.

A genetic approach to hypertension requires attention to the pathophysiologic and biochemical mechanisms that lead from the genotype to the phenotype of high blood pressure. Hypertension itself — as determined by a blood pressure reading — is far removed from gene action, and accurate measurement of blood pressure is dependent on the use of careful techniques. The study of phenotypic effects “closer” to the mechanisms involved in blood pressure regulation is more likely to yield insights into the role of genes that determine high blood pressure.


High Blood Pressure Salt Intake Blood Pressure Regulation Familial Aggregation Intermediate Phenotype 
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© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • A. G. Motulsky
  • W. Burke

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