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Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources |
ONE SIZE DOES NOT FIT ALL:
THE PROMISE OF PHARMACOGENOMICS
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Adverse Drug Reaction. These three simple words convey little of
the horror of a severe negative reaction to a prescribed drug. But
such negative reactions can nonetheless occur. A 1998 study of hospitalized
patients published in the Journal of the American Medical Association
reported that in 1994, adverse drug reactions accounted for more
than 2.2 million serious cases and over 100,000 deaths, making
adverse drug reactions (ADRs) one of the leading causes of
hospitalization and death in the United States. Currently, there
is no simple way to determine whether people will respond well, badly,
or not at all to a medication; therefore, pharmaceutical companies are limited
to developing drugs using a "one size fits all" system.
This system allows for the development of drugs to which the "average"
patient will respond. But, as the statistics above show, one size
does NOT fit all, sometimes with devastating results. What is needed
is a way to solve the problem of ADRs before they happen. The solution
is in sight though, and it is called pharmacogenomics.
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What Is Pharmacogenomics?
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The way a person responds to a drug (this includes both positive
and negative reactions) is a complex trait that is influenced by
many different genes. Without knowing all of the genes involved
in drug response, scientists have found it difficult to develop
genetic tests that could predict a person's response to a particular
drug. Once scientists discovered that people's genes show small
variations (or changes) in their nucleotide (DNA base)
content, all of that changed—genetic testing for predicting drug
response is now possible. Pharmacogenomics is a science that
examines the inherited variations in genes that dictate drug response
and explores the ways these variations can be used to predict whether
a patient will have a good response to a drug, a bad response to
a drug, or no response at all.
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Is there a difference between pharmacogenomics
and pharmacogenetics?
- Pharmacogenomics refers to the general study of
all of the many different genes that determine drug behavior.
- Pharmacogenetics refers to the study of inherited
differences (variation) in drug metabolism and response.
The distinction between the two terms is considered arbitrary,
however, and now the two terms are used interchangeably.
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How Will Gene Variation Be Used in Predicting Drug Response?
DNA sequencing
is the determination of the order of nucleotides (the
base sequence) in a DNA molecule. |
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Right now, there is a race to catalog as many of the genetic variations
found within the human genome as possible. These variations, or
SNPs (pronounced "snips"), as they are commonly called,
can be used as a diagnostic tool to predict a person's drug response.
For SNPs to be used in this way, a person's DNA must be
examined (sequenced) for the presence of specific SNPs. The
problem is, however, that traditional gene sequencing technology
is very slow and expensive and has therefore impeded the widespread
use of SNPs as a diagnostic tool. DNA microarrays (or DNA chips)
are an evolving technology that should make it possible for doctors
to examine their patients for the presence of specific SNPs quickly
and affordably. A single microarray can now be used to screen 100,000
SNPs found in a patient's genome in a matter of hours. As DNA microarray
technology is developed further, SNP screening in the doctor's office
to determine a patient's response to a drug, prior to drug prescription,
will be commonplace.
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How Will Drug Development and Testing Benefit from Pharmacogenomics?
Pre-screening should
allow clinical trials to be smaller, faster, and less expensive;
therefore, the consumer could benefit in reduced drug costs. |
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SNP screenings will benefit drug development and testing because
pharmaceutical companies could exclude from clinical trials those
people whose pharmacogenomic screening would show that the drug being
tested would be harmful or ineffective for them. Excluding these people
will increase the chance that a drug will show itself useful to
a particular population group and will thus increase the chance
that the same drug will make it into the marketplace. Pre-screening
clinical trial subjects should also allow the clinical trials to
be smaller, faster, and therefore less expensive; therefore, the consumer
could benefit in reduced drug costs. Finally, the ability to assess
an individual's reaction to a drug before it is prescribed will
increase a physician's confidence in prescribing the drug and the
patient's confidence in taking the drug, which in turn should encourage
the development of new drugs tested in a like manner.
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What Is NCBI'S Role in Pharmacogenomics?
The explosion in both SNP and microarray data generated from the
human genome project has necessitated the development of a means
of cataloging and annotating (briefly describing)
these data so that scientists can more easily access and use it for
their research. NCBI, always on the forefront of bioinformatics
research, has developed database repositories for both SNP (dbSNP)
and microarray (GEO)
data. These databases include either descriptive information about
the data within the site itself and links to NCBI and external
information resources. Access to these data and information
resources will allow scientists to more easily interpret data that
will be used not only to help determine drug response but to study
disease susceptibility and conduct basic research in population
genetics.
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The Promise of Pharmacogenomics
Right now, in doctors' offices all over the world, patients are
given medications that either don't work or have bad side effects.
Often, a patient must return to their doctor over and over again
until the doctor can find a drug that is right for them. Pharmacogenomics
offers a very appealing alternative. Imagine a day when you go into
your doctor's office and, after a simple and rapid test of your
DNA, your doctor changes her/his mind about a drug considered
for you because your genetic test indicates that you could suffer
a severe negative reaction to the medication. However, upon further
examination of your test results, your doctor finds that you would
benefit greatly from a new drug on the market, and that there would
be little likelihood that you would react negatively to it. A day
like this will be coming to your doctor's office soon, brought
to you by pharmacogenomics.
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GETTING STARTED
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Need help with dbSNP or Map Viewer? How about a quick
"how-to" for using other NCBI data-mining tools?
Try
GETTING STARTED, a new NCBI resource designed to aid
the novice user:
- brief descriptions of data that can be
found/manipulated using a particular NCBI tool
- shortcuts for getting to where you need to go
- concise explanations of NCBI tool graphics with
insider techniques for conducting database searches
- simple examples of tool usage
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Revised: March 31, 2004.
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