<p>Pharmacogenomics And Hypertension: Current Insights</p>

Abstract

Hypertension is a multifactorial disease that affects approximately one billion subjects worldwide and is a major risk factor associated with cardiovascular events, including coronary heart disease and cerebrovascular accidents. Therefore, adequate blood pressure control is important to prevent these events, reducing premature mortality and disability. However, only one third of patients have the effective control of blood pressure, despite several classes of antihypertensive drugs available. These disappointing outcomes may be at least in part explained by interpatient variability in drug response due to genetic polymorphisms. To address the effects of genetic polymorphisms on blood pressure responses to the antihypertensive drug classes, studies have applied candidate genes and genome wide approaches. More recently, a third approach that considers gene-gene interactions has also been applied in hypertension pharmacogenomics. In this article, we carried out a comprehensive review of recent findings on the pharmacogenomics of antihypertensive drugs, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and calcium channel blockers. We also discuss the limitations and inconsistences that have been found in hypertension pharmacogenomics and the challenges to implement this valuable approach in clinical practice.

Pharmacogenomics of Hypertension Treatment

“…Each subclass of calcium channel blocking agent binds at a specific location. For example, dihydropyridines (e.g., amlodipine and nifedipine) exert vascular selectivity, verapamil has cardiac selectivity, and diltiazem can act in both the heart and blood vessels [ 1 , 18 ]. Figure 1 presents the mechanism of CCB’s action.…”

“…Numerous studies have indicated that the single-nucleotide polymorphisms (SNPs) in genes encoding different ion channels, including the large-conductance voltage and calcium-sensitive potassium channel β1 ( KCNMB1 ), the voltage-gated calcium channels α1C ( CACNA1C ), α1D ( CACNA1D ) and β2 ( CACNB2 ), and ERG potassium channel ( KCNH2 ), can modify the antihypertensive responses to CCB and the risk of adverse cardiovascular outcomes [ 1 , 19 , 20 , 21 , 22 , 23 ]. Furthermore, variations in the genes coding the family of HECT domain E3 ubiquitin ligases (NEDD4L) and ATP-binding cassette subfamily B member 1 (ABCB1) have been shown to participate in the regulation of blood pressure (BP) in response to anti-hypertensive drugs [ 11 , 16 ].…”

“…Renin-angiotensin-aldosterone (RAA) system and angiotensin II receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEi) action. The renin–angiotensin system modulates blood pressure and sodium homeostasis through effects that are coordinated via combined mechanisms in the kidney, cardiovascular system, and central nervous system [ 1 , 37 ]. The effects of the renin–angiotensin system are mediated by the renin-related conversion of angiotensinogen into angiotensin I, which is further cleaved by the angiotensin-converting enzyme (ACE) to produce angiotensin II (Ang II).…”

“…Hypertension is one of the strongest modifiable risk factors for cardiovascular diseases, and prevalence is constantly increasing worldwide [ 1 ]. According to estimates, over 116.4 million individuals are suffering from this disease, which is associated with 2303 deaths from cardiovascular disease (CVD) every day [ 2 ].…”

“…According to estimates, over 116.4 million individuals are suffering from this disease, which is associated with 2303 deaths from cardiovascular disease (CVD) every day [ 2 ]. Within the next 20 years, the number of individuals suffering from hypertension is believed to rise by 60% to a total of more than 1.5 billion individuals [ 1 , 3 ]. Currently, 46 percent of U.S. adults are estimated to have hypertension, among whom only 80 percent are aware of their condition, and even fewer follow pharmacological treatment [ 4 , 5 ].…”