[Genetics and essential hypertension: candidate genes or screening of the whole genome?]

Essential hypertension is a major cardiovascular risk factor in the industrialised countries. Its hereditary nature has been well established in many familial studies: about 30% of blood pressure variance is thought to be genetically determined. However, the identification of the culprit genes has met with many difficulties: the multitude of genes, the effect of which is difficult to appreciate, the many possible genetic polymorphisms of each gene studied, the very important role of environmental factors (diet, physical activity, etc...) on the blood pressure itself or on the effect of the genes which control the blood pressure. With the exception of some rare caricatural forms of mendelian transmitted hypertension, the search for genes has focused on large case control studies and/or studies of siblings with hypertension. Two main approaches are used with these collections of subjects. The first consists of analysing so-called "candidate" genes which code for proteins whose function is known and which may influence the blood pressure. In the last ten years, many candidate genes have been assessed with often controversial results. The second approach is to carry out, with no a priori, a complete screen of the genome. These more recent studies have also provided contradictory results. To date, the results illustrate the difficulty of genetic analysis of a complex trait and the necessity of more integrated approaches: analysis of combination of polymorphisms, analysis of a phenotype under standardised environmental conditions, analysis of gene-environment interactions.