Gene markers and antihypertensive therapy.
Increasingly, detailed characterization of human molecular genetic variation will facilitate the use of genetic information in preventing, diagnosing, and treating common diseases. One promising application is the identification of genetic variants influencing responses to drugs used to lower blood pressure (BP) and prevent target-organ complications of hypertension. This update on gene markers to guide antihypertensive therapy highlights polymorphisms recently reported to predict interindividual differences in response to antihypertensive medications. However, single-site variation in most genes makes only a small contribution to differences in BP response, and, after all known genetic and environmental predictors have been considered, most variation in responses still remains unexplained. Advancing beyond our current "trial-and-error" approach to selecting drug therapy in individual patients will undoubtedly require whole-genome approaches to discover additional, novel genetic pathways influencing drug response. In addition, larger samples will be required to more fully characterize genetic variation within candidate genes and to consider the joint effects of gene-gene and gene-environment interactions. Eventually, knowledge of genetic variants that influence BP responses may allow more individualized tailoring of therapy to optimally reduce BP and target-organ damage.