Pharmacogenetics of antihypertensive treatment: detailing disciplinary dissonance

Abstract

Hypertension is a common condition associated with increased cardiovascular morbidity and mortality. In the USA only approximately a third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the unpredictable response individuals have to treatment. Clinicians must often rely on empirical methods to match patients with effective drug treatment. Hypertension pharmacogenetics seeks to find genetic predictors of response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, around 60 studies have investigated associations between genetic polymorphisms and response to antihypertensive drugs. Here we review 18 studies that have been published since 2005. While consonant findings that are insufficient for clinical translation remain the norm, some consistent findings are emerging with several gene-treatment combinations. Nonetheless, differences in study designs, variable methods for assessing pharmacologic exposures, heterogeneous phenotypes (that is, response variables and outcomes ranging from blood pressure to clinical outcomes) and small sample sizes coupled with a short duration of follow-up in many studies account for a large portion of these inconsistencies. Progress in the future will depend upon our ability to launch large studies using high-fidelity phenotyping with multiple drugs and multiple ethnic groups.