Pharmacogenetics of hypertension treatment: a structured review.
The extent of blood pressure lowering by anti-hypertensive agents is difficult to predict for individual patients, even when evaluated in the context of biochemical or demographic information. Genetic predictors (mainly single nucleotide polymorphisms, SNPs) have been the focus of several recent studies and are gaining much attention. We have conducted a literature search for studies in which the lowering of ambient blood pressure by specific drugs or drug classes in humans was related to specific genotypes. Twenty-eight studies were identified, of which six had a single-dose design, and the remaining 22 studied drug effects after more than 4 weeks of drug administration. Virtually all were association studies. Prospective trials that compared the prognostic value of genetic methods to routine clinical practice were not identified. Almost all studies used a candidate-gene design, usually with a very small number of SNPs (typically one). Gene-gene and gene-environment interactions were studied only rarely. Only one study targeted genes involved in drug metabolism. Most candidate-genes were part of the renin-angiotensin system. By far the most extensively studied has been the angiotensin-converting enzyme insertion/deletion polymorphism (15 studies) but, to date, no clear picture has emerged for this or other genetic variants. Thus, the potential for utility of genetic characterization of individual patients as a predictor of anti-hypertensive response has yet to be realized.
Koopmans
Richard P
RP
Department of Pharmacology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.p.koopmans@amc.uva.nl
Insel
Paul A
PA
Michel
Martin C
MC
D000808:Angiotensinogen / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D011945:Receptors, Angiotensin / Q000235:genetics; D000099291:Adducins
D000808:Angiotensinogen; D002148:Calmodulin-Binding Proteins; D019204:GTP-Binding Proteins; D007703:Peptidyl-Dipeptidase A; D018342:Receptors, Adrenergic, beta-1; D011945:Receptors, Angiotensin; D000099291:Adducins