Pharmacogenomics of renin angiotensin system inhibitors in coronary artery disease.
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.
Tsikouris
James P
JP
School of Pharmacy, University of Pittsburgh, 3501 Terrace Street, 808 Salk Hall, Pittsburgh, PA 15261, USA. jpt16@pitt.edu
Peeters
Michael J
MJ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics; D023921:Coronary Stenosis / Q000235:genetics / Q000517:prevention & control; D023381:Endpoint Determination; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D000092502:Renin Inhibitors
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000092502:Renin Inhibitors