Genes and hypertension: where we are and where we should go.
Our understanding of the genetics of hypertension is incomplete. A great deal has, however, been learned about the role of several <<candidate>> genes by altering their expression in transgenic and knockout models. Crosses of inbred strains, analyzed in F2 generations, have demonstrated consistent quantitative trait loci, particularly on chromosomes 1, 2 and 10, suggesting significant contributions of some genes in distinct models of rodent hypertension. The effect of these loci has been tested in congenic strains and their interaction underlined in double congenics. The weakness of testing individual animals from F2 crosses is overcome in recombinant inbred strains. In humans, Mendelian models of hypertension have contributed to progress in our understanding of this disease, but have not yet revealed any major gene of essential hypertension. Many association as well as linkage studies of humans have provided useful though somewhat contradictory data. Our renewed effort is oriented towards the discovery of genetic determinants of environmental interaction in hypertension as well as towards the future of pharmacogenomics. This progress will be the basis of future individualized treatment and prevention.
Hamet
P
P
Centre Hospitalier de l'Université de Montréal-CHUM, Quebec, Canada.
D000818:Animals; D030801:Animals, Genetically Modified; D002875:Chromosomes; D004195:Disease Models, Animal; D004777:Environment; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D051381:Rats
D005819:Genetic Markers