Pharmacogenomics

Adverse Drug Reaction (ADR). These three simple words convey little of the horror of a severe negative reaction to a prescribed drug.
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.

Pharmacogenomics - delivering tailer-made medical treatments>>
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.
pharmacogenomics aims to develop rational means to optimise drug therapy, with respect to the patients' genotype, to ensure maximum efficacy with minimal adverse effects.
Such approaches promise the advent of "personalized medicine", in which drugs and drug combinations are optimised for each individual's unique genetic makeup.

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" Single Nucleotide Polymorphism), 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.

By the way what are SNPs???
Single nucleotide polymorphisms, or SNPs (pronounced "snips"), are DNA sequence variations that occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered. For example a SNP might change the DNA sequence AAGGCTAA to ATGGCTAA. For a variation to be considered a SNP, it must occur in at least 1% of the population. SNPs, which make up about 90% of all human genetic variation, occur every 100 to 300 bases along the 3-billion-base human genome. Two of every three SNPs involve the replacement of cytosine (C) with thymine (T). SNPs can occur in coding (gene) and noncoding regions of the genome. Many SNPs have no effect on cell function, but scientists believe others could predispose people to disease or influence their response to a drug.
Although more than 99% of human DNA sequences are the same, variations in DNA sequence can have a major impact on how humans respond to disease; environmental factors such as bacteria, viruses, toxins, and chemicals; and drugs and other therapies. This makes SNPs valuable for biomedical research and for developing pharmaceutical products or medical diagnostics. SNPs are also evolutionarily stable—not changing much from generation to generation—making them easier to follow in population studies.
Scientists believe SNP maps will help them identify the multiple genes associated with complex ailments such as cancer, diabetes, vascular disease, and some forms of mental illness.
~In addition to pharmacogenomic, diagnostic, and biomedical research implications, SNP maps are helping to identify thousands of additional markers in the genome, thus simplifying navigation of the much larger genome map generated by HGP researchers.

How can SNPs be used as risk factors in disease development?
One thing must be clear that, SNPs do not cause disease, but they can help determine the likelihood that someone will develop a particular illness.

CASE IN POINT

One of the genes associated with Alzheimer's disease, apolipoprotein E or ApoE, is a good example of how SNPs affect disease development. ApoE contains two SNPs that result in three possible alleles for this gene: E2, E3, and E4. Each allele differs by one DNA base, and the protein product of each gene differs by one amino acid.
Each individual inherits one maternal copy of ApoE and one paternal copy of ApoE. Research has shown that

~ a person who inherits at least one E4 allele will have a greater chance of developing Alzheimer's disease. Apparently, the change of one amino acid in the E4 protein alters its structure and function enough to make disease development more likely.

~Inheriting the E2 allele, on the other hand, seems to indicate that a person is less likely to develop Alzheimer's.
Of course, SNPs are not absolute indicators of disease development. Someone who has inherited two E4 alleles may never develop Alzheimer's disease, while another who has inherited two E2 alleles may. ApoE is just one gene that has been linked to Alzheimer's. Like most common chronic disorders such as heart disease, diabetes, or cancer, Alzheimer's is a disease that can be caused by variations in several genes. The polygenic nature of these disorders is what makes genetic testing for them so complicated.