Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Mini Review Horm Res 2009;71:253–259 DOI: 10.1159/000208798 Genetics of Hypertensive Syndrome Alejandro Martinez-Aguayo a Carlos Fardella b a Endocrinology Unit, Department of Pediatrics, and b Department of Endocrinology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile sure regulation. Existing evidence suggests that the ge- netic contribution to blood pressure variation is about 30–50% [1]. However, hypertension is a multifactorial disorder that probably results from the inheritance of a number of susceptibility genes and that involves multiple environmental determinants. The possible candidate genes are components of the renin-angiotensin-aldoste- rone system, adducin, -adrenoceptors, G protein sub- units, regulators of G protein signaling (RGS) proteins, rho kinases, and G protein receptor kinases (OMIM; #145500). Inherited hypertension disorders may be mild, and electrolyte and acid-base abnormalities are often not present. Monogenic hypertension should therefore be in- cluded in the differential diagnosis of any child or ado- lescent with hypertension [2]. In this review, we present the genes involved in blood pressure regulation, and we discuss some associated syndromes. Monogenetic Mineralcorticoid Hypertension Syndromes The term of ‘monogenetic mineralocorticoid hyper- tension’ [3] refers to hypertension that results from a sin- gle genetic mutation causing excessive sodium resorption via the epithelial sodium channel (ENaC) in the distal tubule and collecting duct. This condition is character- ized by suppressed plasma renin activity (PRA) as result Key Words Hypertension  Aldosterone  Familial hyperaldosteronism  Liddle’s syndrome  Glucorticoid resistance  Congenital adrenal hyperplasia Abstract The knowledge of the genetic bases of hypertension has im- proved over the last decade; this area of research has high priority due to the high incidence of hypertension and its impact on public health. Monogenetic mineralocorticoid hypertension syndromes are associated with suppressed plasma renin activity due to excessive activation of the min- eralocorticoid pathway. We review the pathophysiology, phenotype, and method of diagnosis for familial hyperaldo- steronism type I and type II, hypertensive forms of congeni- tal adrenal hyperplasia, 11 -hydroxysteroid dehydrogenase type 2 deficiency, Liddle’s syndrome, an activating mutation of the MR, and glucocorticoid resistance. We also review some genes that could contribute to essential hyperten- sion. Copyright © 2009 S. Karger AG, Basel Introduction Hypertension is the most prevalent, treatable risk fac- tor for diseases of the heart, brain and kidneys. Available evidence suggests a major genetic impact on blood pres- Received: December 8, 2008 Accepted: January 22, 2009 Published online: April 1, 2009 HORMONE RESEARCH Carlos E. Fardella Department of Endocrinology, Faculty of Medicine Pontificia Universidad Católica de Chile Lira 85, piso 5, Santiago (Chile) Tel. +56 02 354 3095, Fax + 56 02 638 5675, E-Mail cfardella@med.puc.cl © 2009 S. Karger AG, Basel 0301–0163/09/0715–0253$26.00/0 Accessible online at: www.karger.com/hre