Personalized Cardiology - Applications of Biotechnology in Cardiovascular Therapeutics - page 315

Chapter 10
Personalized Cardiology
Introduction to Personalized Medicine
Personalized medicine simply means the prescription of specific treatments and
therapeutics best suited for an individual (Jain 2009 ). It is also referred to as individu-
alized or individual-based therapy. Personalized medicine is based on the idea of
using a patient's genotype as a factor in deciding on the treatment options, but other
factors are also taken into consideration. Genomic/proteomic technologies have
facilitated the development of personalized medicines but other technologies are also
contributing to this effort. Application of the principles of personalized medicine to
management of cardiovascular diseases is referred to as “personalized cardiology.”
The constantly growing volume of available data will require an organized inter-
pretation of variations in DNA and mRNA as well as proteins, both on the indi-
vidual and population level. A five-step strategy can be followed when trying to
identify genes and gene products involved in differential responses to cardiovascu-
lar drugs (Siest et al. 2007 ):
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
Gene-environment interactions are important in many human diseases. Genetic
analysis of thousands of transcript abundance traits in human primary endothelial
cell lines in response to proinflammatory oxidized phospholipids implicated in
cardiovascular disease revealed that approximately one third of most regulated
transcripts, showed evidence of gene-environment interactions (Romanoski et al.
2010 ). The interactions resulted primarily from effects of distal-, trans-acting loci,
but a striking example of a local gene-environment interactions interaction was
also observed for FGD6. Some of the distal interactions were validated by siRNA
knockdown experiments. These findings are consistent with the possibility that
gene-environment interactions are responsible, in part, for the failure of association
studies to fully explain common disease variation.