Pharmacogenomics of hypertension.
OBJECTIVE
The emerging field of pharmacogenomics has the potential to fundamentally change the management of essential hypertension, a common, perhaps polygenic syndrome characterized by substantial inter-individual variability in drug responsiveness. As understanding of sequence diversity in the human genome progresses, the prospect grows for tailoring the prescription of antihypertensive drugs to complement common genetic variations among individual patients, allowing optimization of blood pressure control and improved avoidance of drug side effects. Some principles of pharmacogenomics are presented here, along with a review of the most recent literature on genetic determinants of antihypertensive drug responses, with a preview of likely developments to come.


RESULTS
Polymorphisms at candidate pharmacodynamic loci (such as angiotensinogen, angiotensin converting enzyme, and the angiotensin II receptor) have already been shown to predict responses to such specific treatments as angiotensin converting enzyme inhibition and angiotensin II blockade. The National Institutes of Health have established a multi-institutional pharmacogenetics network and knowledge base, whose goals include understanding how common polymorphisms influence therapeutic responses to a variety of drugs, including antihypertensive agents.


CONCLUSIONS
The study of genetic determinants of drug responses, particularly at the pharmacodynamic (drug target/receptor and post-receptor) level, is likely to allow us to more precisely tailor therapy to the individual patient, as well as to promote the creation of novel therapies.
Cadman
Peter E
PE
Department of Medicine and Center for Molecular Genetics, University of California and VA San Diego Healthcare System, 92161, USA.
O'Connor
Daniel T
DT
D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D018807:Polymorphism, Single-Stranded Conformational; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
D000959:Antihypertensive Agents