Pharmacogenetics of antihypertensive treatment

Abstract

Hypertension is a common disorder associated with increased cardiovascular morbidity and mortality. Unfortunately, in the United States, only about one third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the variable and unpredictable response individuals have to pharmacologic treatment. Clinicians often resort to a trial-anderror approach to match patients with effective drug treatment. It is the goal of hypertension pharmacogenetics to apply knowledge of genetic predictors of treatment response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, more than 30 studies have investigated associations between specific genetic polymorphisms and response to particular antihypertensive drugs. Angiotensin-converting enzyme inhibitors have been most frequently studied, followed by diuretics, beta-blockers, angiotensin II blockers, adrenergic alpha-agonists, and calcium channel blockers. Renin-angiotensin-aldosterone system genes have been the most widely studied, with the angiotensinconverting enzyme I/D variant being typed in about one third of all hypertension pharmacogenetic studies to date. In a number of cases, significant and potentially promising associations between genes and drug treatments have been reported. However, taken in sum, the literature suggests that the path from genedrug-outcome association studies to clinically useful knowledge may be neither short nor direct. In the future, carefully designed studies must acknowledge that hypertension is caused by multiple genes and environmental factors that act in concert. These considerations, along with a better understanding of the complexities of the biology of hypertension, open the next set of opportunities for hypertension pharmacogenetics research. Drug Dev.

Clinical Experiences of Intravenous Hydralazine and Labetalol for Acute Treatment of Severe Hypertension in Pregnant Thai Women

“…Apharmacogenetic study of hypertension is still in its infancy. Other factors that may also significantly affect antihypertensive drug response are age, sex, and diet 71 . Although pharmacogenetics provides opportunities to improve drug therapy outcomes, it may increase the complexity of drug prescribing.…”

Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

“…CES1, carboxylesterase 1; CI, confidence interval investigated the effects of genetic variants on the pharmacodynamics of ACE inhibitors [32][33][34][35]. For example, variants in ACE, angiotensinogen, angiotensin receptor 1 and α-adducin 1 have in some studies been associated with the response to ACE inhibitors [36]. However, different studies have yielded conflicting results and further studies are required to clarify the role of genetic variability in the pharmacokinetics and pharmacodynamics of ACE inhibitors.…”

Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study

“…Type 1 angiotensin II receptor (AGTR) is encoded by the AGTR1 gene. AGTR1 polymorphisms are found to be associated with blood pressure response to the inhibition of reninangiotensin system (RAS) in the hypertensive population [16,17]. A1166C (rs5186) SNP of AGTR1 may be involved in posttranscriptional modification and angiotensin II receptor-mediated cell signaling [18].…”

“…A1166C (rs5186) SNP of AGTR1 may be involved in posttranscriptional modification and angiotensin II receptor-mediated cell signaling [18]. A1166C has been extensively studied in hypertension and is associated with the end-point phenotypes [16,17]. Sun et al, found that in Chinese population, A1166C polymorphism of AGTR1 was associated with antihypertensive response to candesartan, and individuals with AC genotype displayed a significantly reduction in SBP after taking candesartan [19].…”