Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources

ONE SIZE DOES NOT FIT ALL:
THE PROMISE OF PHARMACOGENOMICS

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.

What Is Pharmacogenomics?

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.

How Will Gene Variation Be Used in Predicting Drug Response?

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.

How Will Drug Development and Testing Benefit from Pharmacogenomics?

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.

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.

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.