The genetic basis of essential hypertension.
During the last few years the studies on the genetic basis of essential hypertension (EH) have been numerous, allowing however only a partial understanding of the underlying molecular mechanisms. The most used techniques were the candidate gene approach, genome-wide scanning, the intermediate phenotype approach and comparative-genomics in animal models. The renin-angiotensin-aldosterone system may play a prominent role in the genesis of hypertension, and polymorphisms of the genes coding for angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 and 2 receptors, and aldosterone synthase have been widely studied. Other mechanisms may involve the KLK 1 gene of tissue kallikrein, gene variants of endothelial nitric oxide synthase and polymorphisms of the endothelin-1 gene. Finally, a number of studies have highlighted the potential contribution of polymorphisms of genes coding for inflammatory cytokines, adrenergic receptors and intracellular G proteins, which can activate Na+/K+ exchangers. Further important information might derive from proteomic analysis and the study of mitochondrial genome. Overall, results have often been discordant, sometimes suggesting a different expression of the same gene variants in different populations. EH is a highly polygenic condition, caused by the combination of small changes in the expression of many genes, in conjunction with a variable collection of environmental factors.
Puddu
Paolo
P
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
Puddu
Giovanni Maria
GM
Cravero
Eleonora
E
Ferrari
Eleonora
E
Muscari
Antonio
A
D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007610:Kallikreins / Q000235:genetics; D009154:Mutation; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics
D004272:DNA, Mitochondrial; D019332:Endothelin-1; D018343:Receptors, Adrenergic, beta-2; D052250:Nitric Oxide Synthase Type III; D007610:Kallikreins