Genetics in arterial hypertension--clinical and experimental aspects

Genetic approaches provide a new insight into the understanding of biological mechanisms underlying blood pressure regulation and hypertension. Some progress has been made in elucidating the molecular mechanisms of rare forms of hypertension. Common forms of hypertension are likely to be due to combinations of DNA variants of several genes involved in blood pressure regulation. Only little progress has been made in the identification of the underlying genetic factors, due to the complex nature of this disease. Experimental crosses of hypertensive rats offer an ideal setting for the genetic dissection of mammalian physiology. With the opportunity to study inbred rat strains the problem of genetic heterogeneity becomes irrelevant. Cosegregation studies investigating candidate genes for hypertension have been carried out for a number of genes. Moreover, systematic mapping of quantitative trait loci involved in blood pressure regulation has recently become possible in genetically hypertensive rat models. In contrast, genetic studies involving hypertensive individuals are currently limited to the investigation of candidate genes in association and sib-pair analysis. So far, the angiotensinogen gene is the only locus that has been implicated in the pathogenesis of human hypertension in association as well as sib-pair analysis. Considering the complexities of genetic hypertension, animal models will play an important role in the genetic dissection of this disease. A critical prerequisite for the study of human hypertension is the availability of large patient and family cohorts.