Susceptibility genes in hypertension

Abstract

Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have revealed the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium Na reabsorption in the distal nephron, with accompanying expansion of extracellular volume. On the contrary in the essential hypertension the underlying pathogenetic mechanism is more complex because of interplay between several 'risk' genes and environmental factors. It is assumed that blood pressure is under the control of a large number of genes each of which has only relatively mild effects. It has therefore been difficult to discover the genes that contribute to blood pressure variation using traditional approaches including candidate gene studies and linkage studies. Recent development of genotyping technology made large scale genome-wide association studies possible. This approach and the study of monogenic forms of hypertension has led to the discovery of novel and robust candidate genes for human essential hypertension, many of which require functional analysis in experimental models. This review summarizes the current findings for candidate genes associated with blood pressure and focuses on recent advances and future potential of pharmacogenetics of hypertension, with the intent to clarify what amount of these investments in basic science research will be delivered into benefits to patients.