Adverse reactions to medications are a leading cause of hospitalizations and emergency room visits in the United States. As indicated in its name, pharmacogenomics (PGx) is the study of how genes influence the response to a particular drug. Pharmacogenomics combines pharmacology; the study of drug absorption, metabolism, distribution and excretion (ADME) with modern advances in genetic research. With this shift toward personalized medicine, physicians are no longer using a "one size fits all model" to treat patients. Until recently, many drugs adhered to a uniform prescription model and were prescribed or dosed regardless of genetic makeup. Now with increased PGx testing it allows for a more personalized approach to pharmaceutical and therapeutic interventions. Pharmacogenetic targets span a variety of different therapeutic areas including cardiology (warfarin), neurology / psychology (anti-depressants), respiratory (albuterol) and oncology (chemotherapy).
The most notable pharmacogenetic interactions are those with the CYP, SLC6A4 and HTR2A effector proteins. The cytochrome P450 (CYP) genes encode for a family of enzymes that metabolize various therapeutics in order to detoxify the body. These enzymes are most abundant within the liver, however they can be found in various tissues throughout the body. Each specific gene encodes for one of the CYP450 enzymes, and variants within the CYP450 enzymes, which may result in polymorphisms. These polymorphisms in turn reduce or inhibit the metabolic activity of the CYP450 enzymes. Warfarin, a CYP2C9 and CYP34A inhibitor, and carbamazepine, CYP34A inducer, is one of the top 20 most commonly prescribed medications in the US that acts on both of these effector proteins. Polymorphisms in these effector proteins can lead to a decreased efficacy of prescribed medication leading to serious complications and even fatality. Approximately 40% of patients prescribed Warfarin exhibit a delayed effect of the medication due to these polymorphisms. Warfarin is among the top three drugs exhibiting adverse events, accounting for 15% of drug related emergency and hospital visits.
While certain CYP mutations can lead to decreased drug efficacy like warfarin, other mutations can lead to drug toxicity. CYP2D6 enzymes are also part of the cytochrome P450 family of enzymes and play a role in metabolism in a fifth of the drugs currently available. CYP2D6 enzymes are found in SSRIs which make up a common class of antidepressants. Individuals response to SSRIs vary based on their genetic makeup, individuals who poorly metabolize SSRIs are likely to have decreased efficacy to these antidepressants. On the other hand, individuals who are characterized as ultrarapid metabolizers are likely to experience drug toxicity. In either case, emergency care is typically required and can result in fatality. While testing for these polymorphisms is not a standard of care prior to prescribing these medications, testing is becoming more widespread with increased awareness.
Canon BioMedical provides a broad collection of Research Use Only (RUO) PCR genotyping assays for pharmacogenomic research that enable scientists and clinicians to study how the human body metabolizes and responds to drug and therapeutic interventions.
Novallele Genotyping Assays are ideal for obtaining genomic variation results. These assays are designed to test for single nucleotide polymorphisms (SNPs) and small insertions/deletions that have been linked to human biology. The assays are compatible with a rapid PCR protocol followed by High Resolution Melt Analysis (HRMA).
The Novallele Genotyping Assays are recommended to be used in conjunction with Novallele Genotyping Mastermix that is designed to be used with your preferred HRMA-compatible thermocycler. Use the Search Tool below to find a Novallele Genotyping Assay.