Hypertension pharmacogenomics: current status and future directions.

Hypertension is the most common chronic disease in the Western world, and while there are many drug classes from which to choose therapy, only 34% of North Americans currently have their blood pressure controlled. The potential clinical utility of pharmacogenomics in helping to guide antihypertensive drug therapy selection is described. The hypertension pharmacogenetics literature is reviewed, which highlights that only a small fraction of the genes that likely contribute to antihypertensive response have been studied to date. The genes for alpha-adducin (diuretic response), the beta1-adrenergic receptor (beta-blocker response) and angiotensinogen (response to multiple drug classes) are among the genes with the most compelling data (based on replication) as pharmacogenetic candidates. Potential limitations of current studies are also discussed. These include reliance on clinic blood pressure, which is probably a suboptimal response phenotype, and the relatively small sample sizes of most studies to date. Also discussed is the relatively simplistic genetic approach that has been taken, which has focused largely on a single gene or single nucleotide polymorphism within a gene. Multiple ways to overcome these potential limitations are described. Hypertension pharmacogenomics holds tremendous potential for providing a mechanism by which management of hypertensive patients might be improved, and future studies should help move this field towards its clinical potential.