Geneticism of Essential Hypertension

Abstract

T he idea that a person's genetic constitution is allimportant and that genetic knowledge is sufficiently advanced so that we can make judgments on our past or future health was called geneticism by Medawar. 1 He termed geneticism as the application to the human condition of a genetic knowledge or understanding that is assumed to be very much greater than it really is. Proponents of geneticism have promised us that the sequencing of the human genome will offer limitless insights into the pathogenesis of essential hypertension and, moreover, will provide bountiful access to new drug targets and facilitate pharmacological therapy. In terms of citations, only "hypertension and sodium" provokes more "hits" than "hypertension and genetics." Nevertheless, with a few exceptions, the results appear disappointing. We might pause and reflect on the answers to the question, "Why?" In so doing, we should first examine the genetic differences that separate us from one another. The genetic differences between human beings seem to be of 3 types: those based on single gene mutations, those based on polymorphic genetic differences, and those resulting from a complex interaction of many genes.First, there are the differences that divide us into a great majority and a tiny minority. Essential hypertension clearly does not involve a tiny minority and not yet a great majority; however, this state-of-affairs was lost on early students of the subject. When Weitz first proposed the notion of genetic variance on blood pressure, he concluded that essential hypertension was inherited through the actions of a single gene. Because essential hypertension is common, were Weitz correct, we would expect 2 distinct blood pressure distributions in the population, the haves and the have-nots. Indeed, that very argument occupied Platt and Pickering. Platt studied family histories, measured blood pressure in normotensive probands, hypertensive propositi and their relatives, and argued as Weitz did. Pickering et al, however, studied systolic and diastolic blood pressure distributions from the second to eighth decades in first-degree relatives of normotensive probands and hypertensive propositi. 2 They found that the frequency distribution moved upward as age advanced. At no age was there a clear-cut blood pressure distribution into normal and high blood pressures. Moreover, others found subsequently that the relationship between blood pressures of parents and sons was linear for both probands and propositi. As a matter of fact, the relationships were no different than those for height. Pickering concluded that blood pressure is inherited as a graded character over the entire blood pressure range, whether this value is regarded as hypotension, normotension, or hypertension. Nevertheless, disorders that separate us into the great majority and the tiny minority indeed exist. Methods to elucidate these monogenic disorders are at hand and a series of these hypertensive (or hypotensive) disorders have been elucidated. 3

Lack of association between the C825T polymorphism in G-protein beta-3 subunit and arterial blood pressure levels in cardiovascular disease free individuals: the ATTICA epidemiological study

“…Several investigators have issued several nongenetic factors as predictors of hypertension status, like obesity, smoking habits, nutritional habits, physical activity and psychological status. [1][2][3][4][5][6][7] The results from our analysis remained similar, after controlling for several of the aforementioned factors, which enhance the eligibility of our reports.…”

“…1 Polymorphisms in many genes have been implicated for predisposition to hypertension. [2][3][4] Siffert et al 4 first demonstrated a positive relationship between the polymorphism C825T in the GNB3 gene encoding the b3-subunit of heterotrimeric G proteins, with increased levels of blood pressure. However, there are other studies that have failed to show significant results regarding the relationship between the polymorphism C825T in the GNB3 gene and blood pressure levels.…”

Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

“…On the basis of previous arguments and potential functional polymorphisms, [1][2][3][4][5][6][7][8][9][10][11] we hypothesized that genetic polymorphisms in RAS genes, including AGT A-6G, A-20C, G-217A and T174 M, AT1R A1166C and ACE I/D, was associated with the occurrence of EH. The genotype, allele and haplotype frequencies were compared between the hypertensive and normotensive individuals, in an effort to explore the association between the six SNPs of RAS genes and EH in the population of Southern China.…”

“…1 High blood pressure (BP) often leads to a series of pathologies, such as insulin resistance, abnormal metabolism of blood glucose and lipids as well as increased risks of various cerebrovascular and cardiovascular diseases, all of which are detrimental to human health condition. Although the precise aetiology of EH remains unclear, accumulating evidence has suggested that genetic susceptibility is an important factor for the development of EH.…”

Associations SELE Gene Haplotype Variant and Hypertension in Mongolian and Han Populations

“…Essential hypertension (EH), which is characterized by sustained elevated blood pressure (BP) with no identifiable cause, is a public health burden in the worldwide (1) and a complex polygenic disease determined by both genetic and environmental factors (2). A body of evidence suggests that the SELE gene plays an important role in the development and progression of hypertension.…”