Do Genetic Variants of the Renin-Angiotensin System Predict Blood Pressure Response to Renin-Angiotensin System–Blocking Drugs? A Systematic Review of Pharmacogenomics in the Renin-Angiotensin System

• Published in: Current hypertension reports Vol. 13; no. 5; pp. 356 - 361
• Main Author: Konoshita, Tadashi
• Format: Journal Article
• Language: English
• Published: New York Current Science Inc 01.10.2011; Springer Nature B.V
• Subjects: Angiotensin I - antagonists & inhibitors; Angiotensin I - genetics; Angiotensin II - antagonists & inhibitors; Angiotensin II - genetics; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Cardiology; Family Medicine; General Practice; Genetic Variation; Humans; Hypertension; Hypertension - drug therapy; Hypertension - genetics; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Nephrology; Peptidyl-Dipeptidase A - drug effects; Pharmacogenetics; Polymorphism, Genetic; Primary Care Medicine; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - genetics; Pharmacogenetics; RAS; Genetic variant; Direct renin inhibitor; Angiotensin-converting enzyme inhibitor; Angiotensin receptor blocker; Renin-angiotensin system; Blood pressure response; ARB; Renin; ACEI; Polymorphism; Pharmacogenomics; Responder
• ISSN: 1522-6417; 1534-3111; 1534-3111
• DOI: 10.1007/s11906-011-0212-0

The concept of “pharmacogenomics” or “pharmacogenetics” promises to offer the ultimate in personalized medicine, and the renin-angiotensin system (RAS) is one of the most plausible candidates for the application of this approach in the area of hypertension. For the past two decades, genetic variants of the RAS have been tested for association with blood pressure response, but the results have been inconsistent. The problems have been attributed to many issues, but the most fundamental concern is thought to be the statistical power of the studies. Therefore, we have tried to put together a new systematic review using a database search including only recent reports with adequate numbers of subjects, and 11 reports were identified. From the results, we were able to draw conclusions with nearly consistent findings that the conventional genetic variants of the system (i.e., the ACE I/D, AGT M235T, AT1 A1166C, and AT2 variant) are not associated with antihypertensive effects by RAS blockade, at least by one individual SNP. By contrast, significant associations have been reported (by one report each) for AGT rs7079, AT1 haplotype, REN, and ACE2. For these variants, further evaluations and confirmation are anticipated.