Genetics of arterial hypertension and hypotension.
Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na(+) have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the renin-angiotensin-aldosterone system, adducin, beta-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.
Rosskopf
Dieter
D
Department Pharmacology, Research Center for Pharmacology and Experimental Therapeutics, Ernst-Moritz-Arndt-University Greifswald, Friedrich Loeffler Str. 23d, 17487 Greifswald, Germany. dieter.rosskopf@uni-greifswald.de
Schürks
Markus
M
Rimmbach
Christian
C
Schäfers
Rafael
R
D000450:Aldosterone / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007022:Hypotension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D010597:Pharmacogenetics; D018161:Receptors, Mineralocorticoid / Q000378:metabolism
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D006854:Hydrocortisone