145confounding factors. Drug response might be predicted from a certain pattern of
polymorphisms rather than only a single polymorphism, yet these patterns probably
differ between ethnic groups. This could prevent predictions about drug responses
across the general patient population, and it emphasizes the need to stratify clinical
pharmacogenomics studies.
SNP maps and candidate-gene strategies are based on existing knowledge of a
medication’s mechanisms of action and pathways of metabolism and disposition.
The candidate-gene strategy has the advantage of focusing resources on a manage-
able number of genes and polymorphisms that are likely to be important but the
limitations are the incompleteness of knowledge of a medication’s pharmacokinet-
ics and mechanisms of action.
The dynamic complexity of the human genome, involvement of multiple genes
in drug responses, and racial differences in the prevalence of gene variants impede
effective genome-wide scanning and progress towards practical clinical applica-
tions. Genomic technologies are still evolving rapidly, at an exponential pace simi-
lar to the development of computer technology over the past 20 years. Gene
expression profi ling and proteomic studies are evolving strategies for identifying
genes that may infl uence drug response.
Ethical issues also need to be resolved. Holding sensitive information on some-
one’s genetic make-up raises questions of privacy and security and ethical dilemmas
in disease prognosis and treatment choices. After all, polymorphisms relevant to
drug response may overlap with disease susceptibility, and divulging such informa-
tion could jeopardize an individual. On the other hand, legal issues may force the
inclusion of pharmacogenomics into clinical practice. Once the genetic component
of a severe adverse drug effect is documented, doctors may be obliged to order the
genetic test to avoid malpractice litigation.
Pharmacoepigenomics vs Pharmacogenetics in Drug Safety
Phamacoepigenomics refers to drug action as infl uenced by the epigenome, which
is the overall epigenetic state of a cell, and serves as an interface between the envi-
ronment and the genome. The role of epigenetic factors in drug action has been
mentioned throughout this report. The epigenome is dynamic and responsive to
environmental signals not only during development, but also throughout life; and it
is becoming increasingly apparent that chemicals can cause changes in gene expres-
sion that persist long after exposure has ceased. A hypothesis has been presented,
which states that commonly-used pharmaceutical drugs can cause such persistent
epigenetic changes (Csoka and Szyf 2009 ). Drugs may alter epigenetic homeostasis
by direct or indirect mechanisms. Direct effects may be caused by drugs which
affect chromatin architecture or DNA methylation. For example the antihyperten-
sive hydralazine inhibits DNA methylation. An example of an indirectly acting drug
is isotretinoin, which has transcription factor activity. A two-tier mechanism is
Pharmacoepigenomics vs Pharmacogenetics in Drug Safety