Pharmacogenomics of Renin Angiotensin System Inhibitors in Coronary Artery Disease

Abstract

Renin Angiotensin System (RAS) inhibitors comprise some of the most commonly used medications in coronary artery disease (CAD) and its related syndromes. Unfortunately, significant inter-patient variability seems likely in response to these agents; of which, the influence of genetic determinants is of interest. This review summarizes the available RAS inhibitor pharmacogenomic studies which have evaluated RAS polymorphisms that either elucidate mechanism via surrogate endpoint measurements, or predict efficacy via clinical outcomes in CAD related syndromes.Regardless of the endpoint, none of the RAS genotypes conclusively predicts efficacy of RAS inhibitors. In fact, the results of the pharmacogenomic studies were often in direct conflict with one another. Varied results appear due to methodological limitations (e.g., inadequate study power, genotyping error, methods of endpoint measurement), study conceptualization (e.g., overestimating the contribution of polymorphism to disease, lack of haplotype approach), and differences between studies (e.g., genotype frequency, study subject characteristics, the specific medication and dose used). Thus investigators should consider the various methodological limitations to improve upon the current approach to RAS inhibitor pharmacogenomic research in the vast CAD population.

Pharmacogenomics of G Protein-Coupled Receptor Ligands in Cardiovascular Medicine

“…This notion of inconclusive effects of the ACE I/D polymorphism also extends to other indications of ACE inhibitors, such as coronary artery disease and surrogate markers thereof (Tsikouris and Peeters, 2007). In a large study on 2089 Chinese patients with type 2 diabetes, carriers of the II and DI genotypes benefited significantly more from inhibition of the RAAS with regard to development of diabetic nephropathy (So et al, 2006).…”