[Pharmacogenomics and pharmacoproteomics: a strategy for cardio-vascular drugs].
The development of personalized medicine will require improved knowledge of biological variability, particularly concerning the important impact of each individual's genetic makeup. A five-step strategy can be followed when trying to identify genes and gene products involved in differential responses to cardiovascular drugs: 1) Pharmacokinetic-related genes and phenotypes; (2) Pharmacodynamic targets, genes and products; (3) Cardiovascular diseases and risks depending on specific or large metabolic cycles; (4) Physiological variations of previously identified genes and proteins; (5) Environmental influences on them. After summarizing the most well known genes involved in drug metabolism, we used statins as an example. In addition to their economic impact, statins are generally considered to be of significant importance in terms of public health. Individuals respond differently to these drugs depending on multiple polymorphisms. Applying a pharmacoproteomic strategy, it is important to use available information on peptides, proteins and metabolites, generally gene products, in each of the five steps. A profiling approach dealing with genomics as well as proteomics is useful. In conclusion, the ever growing volume of available data will require an organized interpretation of variations in DNA and mRNA as well as proteins, both on the individual and population level.
Siest
G
G
Inserm U525 Equipe 4, Faculté de pharmacie, Université Henri Poincaré Nancy I, 30 rue Lionnois, F 54000 Nancy. gerard.Siest@pharma.uhp-nancy.fr
Marteau
J-B
JB
Maumus
S
S
Berrahmoune
H
H
Jeannesson
E
E
Samara
A
A
Batt
A-M
AM
Visvikis-Siest
S
S
D002317:Cardiovascular Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D010597:Pharmacogenetics; D040901:Proteomics
D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors