As early as 2300 B.C. the Yellow Emperor, a legendary Chinese physician of the Ming Dynasty, made a statement on the cause of high blood pressure that still holds today. He observed that the constant consumption of highly salted foods “makes the pulse hard” and – replacing his graphic description with succinct modern terms – may lead to stroke and aphasia.
Recognising the heart as the centre of circulation is attributed to Aristotle. He apparently was the first to describe heartbeat and pulse as normal constant physiological functions. In Historia animalium Aristotle writes, “The blood in animals pulsates in all the blood vessels throughout [the body] at once” [9].
Human biological and epidemiological research on blood pressure has been conducted for many years, focusing on cross-cultural comparisons, adaptability to certain environmental conditions, and the influences on blood pressure of various cultural and behavioural changes. Field studies began to appear in the literature in the 1920s on such diverse groups as Eskimos, Australian Aborigines, and indigenous African populations [10, 11, 12, 13].
Although the presumably first insight into the cause of elevated blood pressure is now more than 4000 years old, our understanding of the pathogenesis and genetics of hypertension is still incomplete. Indeed, despite enormous progress in our knowledge of abnormalities in gene expression, we have a very unfinished picture of major genetic compounds, i.e. causal genes of hypertension.
Hypertension is a common condition, affecting approximately 20% of the adult population in Westernised society, and is a significant contributor to morbidity and mortality from cardiovascular disease including stroke, myocardial infarction and end-stage renal disease [14]. Essential hypertension is high blood pressure without any obvious cause. Human essential hypertension has a multifactorial origin and is thought to arise from an interaction between susceptibility genes and environmental factors. There is a marked correlation of blood pressure between parents, children and siblings. The relationship between parents and children has been shown in newborns just 5 days after birth [15]. Studies in twins have also shown an agreement in blood pressure with a correlation coefficient of 0.55 – 0.58 in monozygotic twins and 0.25 – 0.27 in dizygotic twins [16].
On the other hand, between spouses, between parents and adopted children, and between natural and adopted children of a family the correlation of blood pressure is either extremely low or nonexistent [17, 18, 19, 20, 21]. Thus, the familial aggregation of essential hypertension is not due to common life styles, e.g. nutrition, but rather to genetically determined factors. Twin and family studies suggest that approximately 30% – 60% of blood pressure variation arises from genes [22]. With the exception of the rare single gene causes (see section 1.1.2) of hypertension where additional biochemical and physiological parameters help to define the link, no clear division is apparent between hypertension and normotension. In fact, blood pressure adopts a normal distribution in the general population and is defined on the basis of thresholds for intervention to reduce blood pressure, and thereby risk of stroke and myocardial infarction (Table 1.1).
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This pattern of blood pressure distribution in the population suggests that there will be several genes involved in the genetic susceptibility to this multifactorial or complex trait [24, 14]. It is possible that genetic variation within an individual gene may have only modest effects on blood pressure unless combined with anomalies within other genes or environmental factors such as sodium in the diet. These inter-relationships may prove difficult to establish for both gene-gene or gene-environment interactions [24]. For example, two genetic variations could interact synergistically to elevate blood pressure substantially more than would be expected from the individual effect of the variants; alternatively, the interaction could be additive, placing an additional increment on blood pressure.
Normal blood pressure is maintained by the physiological interaction of cardiac output and peripheral resistance, and by the control of salt and water balance by the kidney. Despite identifications and understanding of the physiological systems involved in the regulation of blood pressure, it remains unclear which systems are causative for essential hypertension.
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© 2001 Alexander Binder