Does Hypertension Have a Genetic Basis

Introduction
Hypertension is the chronic elevation of blood pressure that can lead to organ failure and even mortality. Cardiac output creates blood pressure but in patients with hypertension, cardiac output is increased. The autonomic nervous system helps to regulate blood pressure but in patients with hypertension, no repinephrine is existent and stress is felt especially acutely.
Phenotype and Genotype
It is unknown what genes cause hypertension. Moreover, as Korner (2010) points out, “their identification is unlikely to be realized with current genetic approaches, because of ambiguities in the genotype-phenotype relationships in these polygenic disorders” (p. 841). Korner (2010) also notes that in the case of hypertension, the phenotype is “not just an aggregate of traits, but needs to be related to specific components of the circulatory control system at different stages” of hypertension (p. 841). Korner (2010) does show that some studies are underway to better understand the genotype-phenotype relationship for hypertension: these studies focus on “major differences in circulatory control in the two main syndromes of EH: (1) stress-and-salt-related EH (SSR-EH)--a constrictor hypertension with low blood volume; (2) hypertensive obesity--SSR-EH plus obesity” (p. 841). Korner (2010) states that each of these differences “is initiated through sensitization of central synapses linking the cerebral cortex to the hypothalamic defense area” and that “several mechanisms are probably involved, including cerebellar effects on baroreflexes” (p. 841). More study needs to be conducted in order to better understand the mechanism however.
Pathophysiological Processes
The pathophysiological processes of hypertension are very complex. The kidney plays an integral role and is also the target organ of the processes while other organs also play a part in the processes. Genetics, neurohormonal systems (sympathetic nervous system, rennin-angiotensin-aldosterone system), along with obesity, and salt intake from diet are all factors in the onset (Hamrahian, 2017).
Hypertension progresses from essential to established stages and typically begins as prehypertension in persons aged 10 to 30 years old and advances to early hypertension in persons aged 20 to 40 years old. Established hypertension typically occurs in people aged 30 to 50 years old.
Hypertension causes vascular tone to be heightened as a result of a-adrenoceptor stimulation and/or increased peptides (angiotension or endothelins). Cytosolic calcium can build up to cause vascoconstriction and can lead to ventricular diastolic dysfunction. It is also hypothesizd that “resetting of pressure natriuresis plays a key role in causing hypertension” and is characterized by parallel shift to high blood pressure along with salt-intensive blood pressure increase (Foex, Phil, Sear, 2004).
Genetic Predispositions
Both hypertension and type 2 diabetes commonly co-exist in a patient and there is some genetic predisposition in these patients for developing cardiovascular disease (Qibin, Forman, Jensen et al., 2012). Geller (2004) shows that both genetics and environment may predispose an individual to hypertension. The genetic factors are not well understood, however (the environmental factors are: salt intake and exercise, for example).
The molecular basis of monogenic disorders that impact blood pressure have received more attention in recent years and a variety of genomic polymorphisms have been linked genetically to hypertensive phenotypes—though the linkage is still unclear to researchers in regards to how the relationship unfolds. However, as Geller (2004) reports, “genome-wide linkage studies have also been performed, and these have linked regions on chromosome 12p and 17q to hypertension in large cohort studies; these loci are intriguing because they have previously been linked to monogenic blood pressure disorders as well. Nevertheless, no precise genetic polymorphism affecting blood pressure has been identified at these sites to date, and so the link between genetic polymorphism and sustained rise in blood pressure remains elusive” (p. 27).
Patterns of Inheritance
The kidney has been shown to be a major factor in inherited forms of hypertension, and as Geller (2004) notes, “the finding that all known inherited and acquired forms of hypertension ultimately operate via the same common pathway has led to the proposal that common forms of hypertension will feature perturbations in this pathway as well” (p. 27). Patterns of inheritance are, however, largely unclear with regards to hypertension, and it is more likely that in families where hypertension is common, environmental factors are also similar. Thus, it is hypothesized that environmental factors play a more significant role in the onset of hypertension at least to some degree.
Genetic Basis
Angiotensinogen (AGT) gene has been associated with hypertension. AGT has been the single most scrutinized gene related to hypertension (Dickson, Sigmund, 2006). AGT serves as substrate to rennin. It is produced in glial celss in the brain and in neuronal populations within nuclei overseeing the cardiovascular function. The kidney expresses similar components to the brain. The studies currently being conducted focus on the role that AGT plays in the relationship between kidney, brain and cardiovascular system.
Genetic Mutation
Inoue, Rohrwasser, Helin et al. (1995) showed that it is possible that a “mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system” (p. 11430), but Dickson and Sigmund (2006) offer that as a result of evolutionary history, “mutations accumulated in the AGT gene that increased circulating AGT levels” (p. 16). Dickson and Sigmund (2006) add that genetic mutation is still unclear, especially as environments have changed so drastically over time: for instance, “the environment in which Westerners now live where salt is replete has changed much faster than evolution, thereby making the ancestral alleles of AGT deleterious in our ‘burger and fries’ environment” (p. 17). This does not, however, rule out the case of there being “relatively recent mutations in such genes that attenuate these deleterious effects in individuals fortunate enough to have the newer alleles” (Dickson, Sigmund, 2006, p. 16).
Current Research
Current research continues to focus on the epidemiology of hypertension, examining genetic as well as environmental factors. It also focuses on medicinal and therapeutic treatments. Shared genetic etiology of hypertension and stroke has received recent attention as well as the impact of smoking on stress physiology in healthy neonates. Risk factors have also been the subject of recent studies on hypertension among researchers.
Racial and Ethnic Predispositions
African-Americans typically have higher blood pressure and are more prone to hypertension than Caucasians. The reason for this may be more environmental than genetic, as the two racial groups typically come from different backgrounds, social environments and face a variety of different pressures.
Risks
Risks associated with hypertension include being over the age of 60, being male, being African-American, having a history of hypertension in the family, being sensitive to salt, being obese, having an inactive lifestyle, engaging in heavy alcohol consumption, and using oral contraceptives.
Interdisciplinary Management Plan
The interdisciplinary management plan to treat the disease includes educating the patient on positive lifestyle changes so as to deter environmental effects (promoting a low salt diet, exercise, cessation of smoking, etc.). Losing weight (through diet and exercise) is part of the plan, as well as implementing methods to manage stress more effectively (breathing methods may be useful for individuals who do not want to use a pharmaceutical treatment).
Recommendations
Recommendations based on current best practice are for patients to limit salt intake, reduce alcohol consumption, smoking, and increase exercise. Weight loss should be a goal and techniques to more effectively manage stress should be implemented.
References
Dickson, M., Sigmund, C. (2006). Genetic basis of hypertension. Hypertension, 48, 14-
20.
Foex, P., Phil, D., Sear, J. (2004). Hypertension: Pathophysiology and treatment.
Continuing Education in Anaesthesia Critical Care & Pain, 4(3), 71-75.
Geller, D. (2004). A genetic predisposition to hypertension? Hypertension, 44, 27-28.
Hamrahian, S. (2017). Pathophysiology of hypertension. Retrieved from
https://emedicine.medscape.com/article/1937383-overview
Inoue I, Rohrwasser A, Helin C, Jeunemaitre X, Crain P, Bohlender J, Lifton RP, Corvol
P, Ward K, Lalouel J-M. (1995). A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system. J Biol Chem., 270, 11430–11436.
Korner, P. (2010). The phenotypic patterns of essential hypertension are the key to
identifying “high blood pressure” genes. Physiological Research, 59(6), 841-857.
Qibin, Q., Forman, J., Jensen, M. et al. (2012). Genetic predisposition to high blood
pressure associates with cardiovascular complications among patients with type 2 diabetes. Diabetes, 61(11), 3026-3032.