The human genome consists of about 30,000 genes comprised of billions of nucleotides.
Although the DNA of any two different persons is 99% identical, variant sequences
can and do occur in individuals. Variants that are found in more than 1% of the population
are called polymorphisms, of which the most common type is the single nucleotide polymorphism
(SNP). Deletion, insertion, and tandem repeats are other types of polymorphisms collectively
termed copy number variations (CNVs). The role of inheritance in individual variation
to drug response has been studied extensively; when applied to specific genes it has
been called pharmacogenetics (PGt), and when applied to the whole genome it has been
referred to as pharmacogenomics (PGx). For the purposes of this review, the terms
PGx and PGt are used interchangeably.
1
Many excellent reviews have been published on various aspects of PGx. Implementation
of PGx from a laboratory perspective,
2
various clinical interpretation guidelines,
3
,
4
,
5
,
6
as well as PGx as applied to clinical therapeutics in various specialties of medicine
has been discussed.
7
,
8
,
9
Most of these reviews cover the therapeutic use of a pharmacologic drug/marker combination.
However, occasionally the body's response to the drug is toxicity, possibly caused
by an adverse drug reaction due to the interindividual variations in drug response.
KEY POINTS
- •Pharmacogenomics is a useful tool in clinical toxicology for the characterization of many gene polymorphisms associated with different pharmacokinetics or pharmacodynamics of exogenously administered drugs.
- •These genetic variants may determine ranges of variation in such fundamental aspects as drug-metabolizing enzymes, drug transporters, drug receptors, or targets of drug action.
- •Toxicologically significant drugs for which the FDA has required the manufacturer to identify relevant pharmacogenomics markers on the label include carisoprodol, citalopram, codeine, and risperidone.
- •CYP2D6 variant alleles can result in four metabolic phenotypes—ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, and poor metabolizers—that demonstrate significant differences in opiate metabolism.
- •For personalized medicine, combining pharmacogenomics testing with therapeutic drug monitoring may allow the identification of individuals who need lower or higher doses, or even a different drug.
Key Words
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Article info
Footnotes
The authors have nothing to disclose.
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© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
