학술논문

Pharmacogenomics and cardiovascular drugs: Need for integrated biological system with phenotypes and proteomic markers
Document Type
Academic Journal
Source
European Journal of Pharmacology. Dec 19, 2005 527(1):1-22
Subject
Language
English
ISSN
0014-2999
Abstract
ABSTRACT: Personalized medicine is based on a better knowledge of biological variability, considering the important part due to genetics. When trying to identify involved genes and their products in differential cardiovascular drug responses, a five-step strategy is to be followed:After summarizing the most well-known genes involved in drug metabolism, we will take as example of drugs, the statins, considered as very important drugs from a Public-Health standpoint, but also for economical reasons. These drugs respond differently in human depending on multiple polymorphisms. We will give examples with common ApoE polymorphisms influencing the hypolipemic effects of statins. These drugs also have pleiotropic effects and decrease inflammatory markers. This illustrates the need to separate clinical diseases phenotypes in specific metabolic pathways, which could propose other classifications, of diseases and related genes.Hypertension is also a good example of clinical phenotype which should be followed after various therapeutic approaches by genes polymorphisms and proteins markers.Gene products are under clear environmental expression variations such as age, body mass index and obesity, alcohol, tobacco and dietary interventions which are the first therapeutical actions taken in cardiovascular diseases. But at each of the five steps, within a pharmacoproteomic strategy, we also need to use available information from peptides, proteins and metabolites, which usually are the gene products. A profiling approach, i.e., dealing with genomics, but now also with proteomics, is to be used.In conclusion, the profiling, as well as the large amount of data, will more than before render necessary an organized interpretation of DNA, RNA as well as proteins variations, both at individual and population level.