Genetic determinants of blood pressure regulation

Abstract

Hypertension is a multifactorial disorder that probably results from the inheritance of a number of susceptibility genes and involves multiple environmental determinants. Existing evidence suggests that the genetic contribution to blood pressure variation is about 30-50%. Although a number of candidate genes have been studied in different ethnic populations, results from genetic analysis are still inconsistent and specific causes of hypertension remain unclear. Furthermore, the abundance of data in the literature makes it difficult to piece together the puzzle of hypertension and to define candidate genes involved in the dynamic of blood pressure regulation. In this review, we attempt to highlight the genetic basis of hypertension pathogenesis, focusing on the most important existing genetic variations of candidate genes and their potential role in the development of this disease. Our objective is to review current knowledge and discuss limitations to clinical applications of genotypic information in the diagnosis, evaluation and treatment of hypertension. Finally, some principles of pharmacogenomics are presented here along with future perspectives of hypertension.

Association of High Altitude Hypertension with Angiotensin Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism

“…Human essential hypertension accounts for 90% of the hypertensive population, is a complex multifactorial and polygenic disorder [1,2] affecting large groups with a genetic heritability ranging from 15% to 35% [3][4][5][6]. The interplay between environmental and genetic factors is a major determinant of the final phenotype in hypertension [2].…”

Complex haplotypes derived from noncoding polymorphisms of the intronless α 2A -adrenergic gene diversify receptor expression

“…These include inhibition of neurotransmitter release from presynaptic nerves, inhibition and stimulation of postsynaptic central nervous system signaling pathways, inhibition of lipolysis in adipocytes, stimulation of platelet aggregation, and inhibition of insulin secretion from pancreatic islet cells (1). Familial clustering of phenotypes and ethnic variability are observed in a number of diseases associated with aberrancies of the above physiologic responses, including heart failure, hypertension, and obesity (2)(3)(4). And in familial syndromes such as the familial cardiomyopathies reduced penetrance and generation skipping are not common (2,5).…”

The pressure of finding human hypertension genes: new tools, old dilemmas

“…6 Hundreds of studies performed so far have produced overwhelmingly inconsistent results. 15,16 Thus, despite high expectations, the contribution of most of the candidate association studies to the understanding of hypertension and its genetic determinants has been modest. One explanation for the lack of success of this strategy to dissect the genetic background of hypertension may be related to an incorrect a priori assumption that predisposition to hypertension is driven by genes encoding classical BP regulators such as angiotensinogen or endothelin-1.…”