What is Pharmacogenomics?
Pharmacogenomics is the study of how genes affect a person's response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person's genetic makeup.
Many drugs that are currently available are "one size fits all," but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will have negative side effects (also called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body's response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions.
Personalized medicine is a term that has been applied to clinical practice when a doctor uses genetic information in addition to other information about a person's physical exam, medical history, age, race, and sex in order to identify the right drug and dose for each individual. Although personalized medicine and pharmacogenomics are still in their infancy, certain drug-gene interactions are already established, and this information is starting to be used in clinical practice.
What is Drug Response Testing?
Studies have suggested that 50% or less of medications are effective. Even though individual differences in drug response can result from the effects of age, sex, disease, liver and kidney functioning and/or drug-drug interactions, genetic factors also influence both the effectiveness of the drug as well as negative side effects.
Researchers are working to identity the enzymes (and the genes that code for these enzymes) involved in drug metabolism. We already know that the cytochrome P450 family of liver enzymes is responsible for breaking down (metabolizing) more than 30 different classes of drugs, and about 50% of medications on the market are associated with three enzymes in this family: 2D6, 2C9, and 2C19. These enzymes are also commonly referred to as cytochrome P450 2D6 (CYP2D6), cytochrome P450 2C9 (CYP2C9) and cytochrome P450 2C19 (CYP2C19). These enzymes are produced by three genes: CYP2D6, CYP2C9, and CYP2C19, respectively. Genetic variations in these three genes can therefore affect their associated enzyme's ability to metabolize medications involved in the 2D6, 2C9 and 2C19 pathways.
- CYP2D6: Affects about 25% of medications in clinical use (including Paxil, Strattera, codeine, Abilify and Tamoxifen)
- CYP2C9: Affects about 5-10% of medications in clinical use (including Warfarin, ibuprofen [Advil and Motrin], Dilantin, and Celebrex)
- CYP2C19: Affects about 15% of medications in clinical use (including Prilosec, Prozac, Valium and Prevacid)
Other enzymes in the cytochrome P450 family as well as other metabolic pathways have also been identified. Some of these enzymes and their associated genes are better studied than others. Click here to see a list of medications involved in the 2D6, 2C9 and 2C19 pathways.
What Testing Tells You
Positive: A positive testing result indicates that the individual may either be a "poor metabolizer" (people with no enzyme activity) or an "ultra metabolizer" (people with elevated enzyme activity). This can affect how a person responds to medications associated with the enzyme, whether they experience negative side effects, as well as their risk for drug-drug interactions when they are taking multiple medications at once.
Negative: A negative testing result indicates that the individual most likely will have a "normal" (standard) response to the standard dose of medication. Of note, a normal testing result does not guarantee that a medication will be effective. Some of the other factors that may also affect drug response include age, sex, liver and kidney functioning, other medications, environment, lifestyle as well as other yet to be identified enzymes and their associated genes.
Ethnicity and the Cytochrome P450 Genes
Genetic variations in the cytochrome P450 genes are more common in some ethnic groups than others.
- CYP2D6: About 5-10% of Caucasians, 2% of Asians, and 2-7% of African-Americans are "poor metabolizers." People of Saudi Arabian ancestry have a 20% chance to be "ultra metabolizers," while people of Ethiopian ancestry have a 30% chance to be "ultra metabolizers."
- CYP2C9: About 2-8% of Asians, 5-10% of Caucasians and 3-13% of African-Americans are "poor metabolizers."
- CYP2C19: About 13-23% of Asians, 3-5% of Caucasians and 3-5% of African-Americans are "poor metabolizers."
Drug Response Testing Considerations
Here are some considerations that may be useful when considering drug response testing:
- Have you experienced several negative side effects when taking a medication? Do you have a family history of adverse negative reactions?
- Do certain drugs not seem to work for you?
- Are you from an ethnic group that has a high chance to be a "poor metabolizer" or an "ultra metabolizer"?
- Do you have a chronic health condition and need to take medication for an extended period of time?
- Do you plan to take a medication with an FDA labeling about genetic information? The FDA has begun including genetic information on some drug labels so that patients and health care professionals can have current information on how genetics, along with other factors can influence a person's response to a particular drug. Currently, about 10% of the drug labels approved by the FDA include genetic information and this number continues to increase.
Drug Response Testing Providers
Drug Response Testing laboratories have different standards and policies, which should always be reviewed before ordering.
In general, the majority of providers offer a Cytochrome 450 Drug Response Panel for common variations in three major cytochrome P450 genes: CYP2D6, CYP2C9 and CYP2C19.
Some providers offer an Expanded Drug Response Panel that involves additional genes associated with the cytochrome P450 system and/or other metabolic pathways (such as CYP1A2 and NAT2).
Some providers offer drug response testing that is medication specific. Some of these tests involve some of the cytochrome P450 genes, while others involve genes associated with other metabolic pathways.
- Abacavir Response Testing looks for HLA-B*5701 variant associated with hypersensitivity to the drug. The hypersensitivity reaction can have serious, life-threatening effects on multiple organ systems.
- Acid Reflux & Ulcer Medication Response Testing looks for variants in two of the cytochrome P450 genes, CYP2C9 & CYPC19. This testing may be appropriate for anyone who is currently taking or considering taking medications to treat or prevent acid reflux or ulcers.
- Asthma Treatment Drug Response Testing looks for a particular variation (arg16) in the ADRB2 gene that has been shown in several studies to alter the body's response to beta-agonists, a type of medication used to treat asthma. Beta-agonists include albuterol, salbutamol, and salmeterol. We all have two copies of the ADRB2 gene. A little less than 20% of the U.S. general population has two copies of this variation, one in each gene. The effectiveness of albuterol as a rescue therapy may be reduced in these individuals when beta-agonists are used as a routine treatment for asthma.
- Camptosar (irinotecan) Response Testing looks for a variant (*28) in the UGT1A1 gene that increases an individual's risk of developing severe neutropenia, a condition that negatively impacts the immune system, when taking irinotecan. Camptosar is used to treat cancers of the colon and rectum.
- Carbamazepine Response Testing looks for two genetic markers in the HLA region that are associated with the HLA-B*1502 variant. This variant is associated with hypersensitivity to the drug and increases an individual's risk of developing a life-threatening skin disorder.
- Clopidogrel (Plavix®) Response Testing looks for variants in one of the cytochrome P450 genes, CYPC19. This testing may be appropriate for anyone who is currently taking or considering taking plavix.
- Clozapine Response Testing looks for a genetic variation that has been shown to influence an individual's risk of developing clozapine-induced agranulocytosis compared to the untested population. Clozapine is a medication commonly used to treat schizophrenia.
- Depression Medication Response Testing looks for variants in two of the cytochrome P450 genes, CYP2C9 & CYPC19. This testing may be appropriate for anyone who is currently taking or considering taking anti-depressants.
- Diabetes Medication Response Testing looks for variants in two of the cytochrome P450 genes, CYP2D6 & CYPC19. This testing may be appropriate for anyone who is currently taking or considering taking oral hypoglycemic medications.
- DPD Enzyme Testing for Fluorouracil (5-FU) looks for a genetic variation that causes a deficiency of an enzyme called dihydropyrimidine dehydrogenase (DPD). This enzyme is important in the metabolism and deactivation of 5-FU, a chemotherapy medication commonly used in the treatment of breast, colon, and skin cancer. People with this variation are at increased risk to have severe toxic reactions to 5-FU.
- Epilepsy Medication Response Testing looks for variants in two of the cytochrome P450 genes, CYP2C9 & CYPC19. This testing may be appropriate for anyone who is currently taking or considering taking anti-epileptic medications.
- Hodgkin's/Non-Hodgkin's Lymphoma Drug Response Treatment Testing looks for a genetic variation that has been shown to influence an individual's response to Rituximab, a medication commonly used to treat non-Hodgkin's lymphoma.
- Methotrexate Response Testing looks for a variant in the MTHFR gene associated with toxicity to the drug.
- Statin-Induced Myopathy Testing looks for a variant in the SLCO1B1 gene that increases an individual's risk of developing degenerative muscle disease (myopathy) when taking statins.
- Tamoxifen Response Testing looks for variants in the CYP2D6 gene. This testing may be appropriate for postmenopausal women who are currently taking or considering taking tamoxifen to help prevent the recurrence of breast cancer.
- Warfarin (Coumadin®) Response Testing looks for variants in two genes, CYP2C9 & VKORC1. The VKORC1 gene variant is only known to affect a person's response to warfarin and is not currently associated with any other medications. This testing may be appropriate for anyone who is currently taking or considering taking warfarin.
Drug Response testing is widely available online (over the internet). Go to the Tests tab to link to online providers, compare providers, and read provider reviews.