INTRODUCTION
What is pharmacogenomics
History
Principle
So what’s new about pharmacogenomics?
single nucleotide polymorphism (SNP)?
Genes commonly involved in pharmacogenomic drug metabolism and response
The anticipated benefits of pharmacogenomics
Pharmacogenetics Research/Database Program
Some of the barriers to using pharmacogenomics
Conclusion
References
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Pharmacogenomics, by kk sahu
1. By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )
2. SYNOPSIS:-
INTRODUCTION
What is pharmacogenomics
History
Principle
So what’s new about pharmacogenomics?
single nucleotide polymorphism (SNP)?
Genes commonly involved in pharmacogenomic drug
metabolism and response
The anticipated benefits of pharmacogenomics
Pharmacogenetics Research/Database Program
Some of the barriers to using pharmacogenomics
Conclusion
References
3. INTRODUCTION
•Pharmacogenomics is the branch of pharmacology which deals
with the influence of genetic variation on drug response in
patients by correlating gene expression or single-nucleotide
polymorphisms with a drug's efficacy or toxicity.
•It aims to develop rational means to optimize drug therapy, with
respect to the patients genotype, to ensure maximum efficacy
with minimal adverse effects.
•Pharmacogenomics is the whole genome application of
pharmacogenetics, which examines the single gene interactions
with drugs.
4. What is pharmacogenomics?
Pharmacogenomics means “Pharma” = drug or medicine
“Genomics” = the study of genes.
Pharmacogenomics is the study of how genes affect a
person’s response to drugs.
The emerging field of pharmacogenomics arises from the
convergence of advances in pharmacology, genetics, and
more recently genomics.
Pharmacogenomics combines traditional pharmaceutical
sciences such as biochemistry with annotated knowledge of
genes, proteins, and single nucleotide polymorphisms.
5. History
•Genomics was established by Fred Sanger when he first
sequenced the complete genomes of a virus and a
mitochondrion.
•His group established techniques of sequencing, genome
mapping, data storage, and bioinformatic analyses in the 1970-
1980s.
•The first free-living organism to be sequenced was that of
Haemophilus influenzae in 1995, and since then genomes are
being sequenced at a rapid pace.
•As of September 2007, the complete sequence was known of
about 1879 viruses, 577 bacterial species and roughly 23
eukaryote organisms.
6. principle
• “Pharmacogenomics” is the study of how individual genetic
differences affect drug response.
• This definition encompasses inter individual genetic
differences such as variation in DNA sequence, gene
expression, and copy number related to an individual’s
metabolism of drugs (pharmacokinetics) or physiological
response to drugs (pharmacodynamics).
• Researchers in this field study genes that produce drug
metabolizing-enzyme in the body.
• In some cases, an active drug is made inactive or less active
through metabolism.
7.
8. So what’s new about
pharmacogenomics?
The field of pharmacogenomics really developed
only in the last 15 years because of new technology
for the large-scale and high-speed collection of data,
for measuring DNA sequence variations, especially
single nucleotide polymorphisms (SNPs), and drug
responses, especially mRNA expression analysis
using microarrays.
9. single nucleotide polymorphism
(SNP)?
It is variability in a single nucleotide (A, C, G,
or T) within an otherwise fixed DNA
sequence, where a certain fraction of the
population have one nucleotide (say C) and
another fraction of the population have
another nucleotide (say T).
10. What is a single nucleotide
polymorphism (SNP)?
It is variability in a single nucleotide (A, C, G, or T)
within DNA sequence.
……. G G T A A C T G ……
……. G G C A A C T G …...
SNPs are very common in the human population.
Between any two people, there is an average of one SNP every ~1250
bases.
Most of these have no phenotypic effect
11. How do I know this? By
searching the NIH databases,
as follows:
12.
13.
14.
15.
16.
17.
18. Single Nucleotide Polymorphisms (SNPs)
A key to human variability
Functional but altered proteinFunctional protein
DNA sequence variation at a single nucleotide that may alter the
function of the encoded protein
Polymorphisms are common and contribute to common diseases and
influence our response to medications
19. Genes commonly involved in pharmacogenomic drug
metabolism and response
• There are several genes responsible for differences in drug
metabolism and response.
• Among the most common are the Cytochrome P450 (CYP)
genes, encoding enzymes that control the metabolism of
more than 70 percent of prescription drugs.
• People who carry variations in certain CYP genes often do
not metabolize drugs at the same rate or extent as in most
people, and this can influence response in many ways.
20.
21. The anticipated benefits of pharmacogenomics
• More Powerful Medicines
Pharmaceutical companies will be able to create drugs based
on the proteins, enzymes, and RNA molecules associated
with genes and diseases.
• Advanced Screening for Disease
Knowing one's genetic code will allow a person to make
adequate lifestyle and environmental changes at an early age
so as to avoid or lessen the severity of a genetic disease.
• More Accurate Methods of Determining Appropriate
Drug Dosages
Current methods of basing dosages on weight and age will be
replaced with dosages based on a person's genetics --how
well the body processes the medicine and the time it takes to
metabolize it.
22. • Better Vaccines
Vaccines made of genetic material, either DNA or RNA,
promise all the benefits of existing vaccines without all
the risks.
• They will activate the immune system but will be
unable to cause infections.
• Decrease in the Overall Cost of Health Care
Decreases in the number of adverse drug reactions, the
number of failed drug trials, the time it takes to get a
drug approved, and an increase in the range of possible
drug targets will promote a net decrease in the cost of
health care.
23. Is pharmacogenomics in use
today?
Today, clinical trials researchers use genetic tests for
variations in cytochrome P450 genes to screen and
monitor patients.
Today, doctors can use a genetic test to screen
patients for this deficiency, and the TMPT
(thiopurine methyltransferase) activity is monitored
to determine appropriate thiopurine dosage levels.
24. Overview of the NIH’s
Pharmacogenetics
Research/Database Program
In 1999, the General Medical Sciences unit of the NIH
(NIGMS) announced its intention to create a
pharmacogenetics research network and database
program.
• Stanford Medical Informatics was one of the
organizations that received funding to create the
database portion of the system, dubbed the PharmGKB
(http://www.nih.gov/grants/guide/rfa-files/RFA-
GM-99-004.html ; Pharmacogenetics
Knowledge Base).
25. The NIGMS is providing funding for studies of several gene
systems that are known to be important in determining drug
response. Its targets include the following:
•The cytochrome P450 system
•The transferases of the so-called phase 2 metabolism, sulfylation
and methylation systems
•Transporters of molecules, which are critical for (1) moving drugs
out of the gastrointestinal system and through the kidneys and (2)
transporting compounds into cells so as to provide pharmacologic
activity
•Steroid receptors
•Intercellular signal transduction elements
•Cell surface receptors, such as beta receptors that respond to
beta agonists
26. In addition to Stanford Medical Informatics’ work on the PharmGKB,
participants in the NIH’s pharmacogenetics program include the
following institutions, which are handling differing aspects of this effort:
•University of California–San Francisco (Giacomini): transporter
molecules
•University of Chicago (Ratain): anticancer agents
•Georgetown University (Flockhardt): tamoxifen as a model system for
other steroids and steroid family agonists
•Brigham and Women's Hospital (Drazen): three pathways of asthma—
beta agonists, steroids, and leukotrienes
•University of California–Los Angeles (Licinio): depression
•Houston (Rothstein): a lawyer analyzing the legal implications of
pharmacogenetics research
•Yale University (Nadkarni): informatics, looking at the infrastructure
behind the pharmacogenetics knowledge base
27. Pharmacogenomics in future
New developments in this field will impact on
drug design at three main levels:
(1)the interaction of the drug with its receptor
binding site;
(2) the absorption and distribution of the drug;
(3) the elimination of the drug from the body.
28. Some of the barriers to using pharmacogenomics
Pharmacogenomics is a developing research field that is still in its
infancy. Several of the following barriers will have to be overcome
before many pharmacogenomics benefits can be realized.
•Complexity of finding gene variations that affect drug response
Single nucleotide polymorphisms (SNPs) are DNA sequence
variations that occur when a single nucleotide (A,T,C,or G) in the
genome sequence is altered.
• Limited drug alternatives - Only one or two approved drugs may
be available for treatment of a particular condition.
• Disincentives for drug companies to make multiple
pharmacogenomic products - Most pharmaceutical companies
have been successful with their "one size fits all" approach to drug
development.
29. Conclusion
• Pharmacogenomics in pharmaceutical industry
is a potential tool.
• The main aims of it are; personalized therapy,
improvement in efficacy and reduction in
adverse drug reactions, correlation of genotype
with clinical genotype, identification of novel
targets for new drugs, and pharmacogenetic
profiling of patients to predict disease
susceptibility and drug response.
30. References
• David W.Mount(2004) Bioinformatics :sequence and
genome analysis. Second edition.
• Internet: http://www.genetics.edu.au