Genetics of essential hypertension: from families to genes.

Family studies demonstrated the contribution of genetic factors to the development of primary hypertension. However, the transition from this phenomenologic-biometric approach to the molecular-genetic one is more difficult. This last approach is mainly based on the Mendel paradigm; that is, the dissection of the poligenic complexity of hypertension is brought about on the assumption that the individual genetic variants underlying the development of hypertension must be more frequent in hypertensive patients than in controls and must cosegregate with hypertension in families. The validity of these assumptions was clearly demonstrated in the so-called monogenic form of hypertension. However, because of the network of the feedback mechanisms regulating BP, it is possible that that the same gene variant may have an opposite effect on BP according to the genetic and environmental backgrounds. Independent groups of observations (acute BP response to saline infusion, incidence of hypertension in a population follow-up of 9 yr, age-related changes on BP) discussed in this review suggest a positive answer to this question. Therefore the impact of a given genetic variant on BP level must be evaluated within the context of the appropriate genetic epistatic interactions. A negative finding or a minor genetic effect in a general population may become a major gene effect in a subset of people with the appropriate genetic and environmental backgrounds.