Genetics of human arterial hypertension: Three approaches to analyse a complex trait

Human arterial hypertension is a complex trait, partly determined by genetic factors. From the analysis of familial studies, it has been estimated that approximately 30 % of the blood pressure variance within a population was of genetic origin. Three main types of human studies have been undertaken to try to identify susceptibility genes to hypertension. The first one corresponds to the systematic analysis of the so-called candidate genes, i.e. genes encoding proteins, enzymes, receptors, which are known to belong to pathways controlling blood pressure. Up to now, the more interesting results have been obtained on genes encoding the renin angiotensin system, the a adducin, the G protein subunit beta3, and adrenergic receptors. The genome wide scan approach corresponds to a. systematic analysis of evenly spaced markers throughout the genome in sibling pairs or in more complex families. This second strategy has shown that there was hot a single locus that was regularly found by several studies, but rather several possible loci which most often have not been replicated from one study to another one. Among those, the long arm of the human chromosome 17 (17q12-q21) is in synteny with a blood pressure locus found in spontaneously hypertensive rats. The third approach, up to now the most successful, corresponds to the identification of major genes involved in rare mendelian forms of hypertension. For example, genes responsible for Liddle syndrome, glucocorticoid remediable aldosteronism, apparent mineralocorticoid excess have been characterized and have demonstrated the importance of sodium and water homeostasis in blood pressure control.