title: Pharmacogenetics of antihypertensive treatment.
abstract: Hypertension is a common disorder associated with increased cardiovascular morbidity and mortality. Unfortunately, in the US only about one-third of those who are aware of their hypertensive status have their blood pressure adequately controlled. One reason for this is the variable and unpredictable response individuals have to pharmacologic treatment. Clinicians often resort to "trial-and-error" to match patients with effective drug treatment. Hypertension pharmacogenetics seeks to find genetic predictors of drug response. To date, more than forty studies have investigated associations between genetic polymorphisms and response to antihypertensive drugs. Angiotensin-converting enzyme inhibitors and beta blockers have been most frequently studied, followed by angiotensin II blockers, diuretics, adrenergic alpha-agonists, and calcium channel blockers. Renin-angiotensin-aldosterone system genes have been the most widely studied, with the angiotensin-converting enzyme I/D variant being typed in about one-half of all hypertension pharmacogenetic studies. In total, 160 possible gene polymorphism-drug interactions have been explored, with about one-quarter of these showing that genes predict drug response. However, disparate and conflicting findings have been the rule rather than the exception, and the discovery of clinically relevant antihypertensive drug-response genes remains elusive. While there is a growing enthusiasm that pharmacogenetics of hypertension is important, the translation of pharmacogenetic findings to clinical practice in the future will depend on additional studies to enhance our pharmacogenetics knowledge base, the availability of pharmacogenetic screening tests that are affordable and easy to implement in clinical practice, a cohort of clinicians who are trained to interpret genetic test results, and health care systems that pay for them. Caution regarding the future of hypertension pharmacogenetics is warranted.
authors.affiliation: Department of Epidemiology, University of Alabama, RPHB 220E, 1530 3rd Avenue South, Birmingham, 55294-0022, USA. arnett@uab.edu
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Steven A
authors.initials: SA
authors.lastname: Claas
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Glasser
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D004232:Diuretics / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D007703:Peptidyl-Dipeptidase A