Your Genes your drugrepsonse1Just as we differ in appearance, behavior, and likelihood to develop disease, so too does our likely response to prescription drugs. Often a medication will prove effective for one person, while simultaneously ineffective for another person. Further, sometimes a medication presents no side effects in one person, while it could prove toxic for another. Medication side effects are common; approximately 5% of hospital stays are related to life-threatening side effects1. More than 2 million serious adverse drug reactions result in 100,000 deaths annually. Adverse drug reactions are the 4th leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents and automobile deaths2.

Some adverse drug reactions are caused by genetic variation in genes that regulate how drugs are processed in the body. The study of genetic variation and how people respond to medications is called pharmacogenomics, often abbreviated PGx. DNA tests can reveal which personalized medicine can help individuals find the right medication for them.

The use of pharmacogenomics by doctors and pharmacists to select the right dose of the right medication for a person is currently limited. Cancer treatment is the field of medicine currently utilizing pharmacogenomics for dosing. It is now common when treating certain cancers to test the tumor tissue for its genetic “signature” and use this information to choose the most effective treatment based on that tumor’s specific genetic makeup. This approach has been successfully adopted in leukemia and breast cancer treatment.

Recently, more commonly prescribed medications have been shown to be affected by common genetic variants. Examples include Coumadin® (Warfarin), a blood thinner used to prevent blood clots, and Plavix® (Clopidogrel), an antiplatelet medication used to prevent future heart attacks and strokes. The Coriell research study currently provides risk reports to study participants illustrating the influence of their genetics on their likely response to Plavix®. The goal of personalized medicine is to routinely use a person’s genetic information to decide what medication to prescribe and at what dose. This personalized approach has the potential to reduce or eliminate drug side effects.

In most cases, how a person responds to a medication is not based on a single genetic variant. Instead, medication response is usually based on a specific combination of genetic variants in or near a gene (called a haplotype). There can be many different combinations of variants for each gene. To distinguish one combination of variants from another, scientists sometimes use a numbering system. For example: one combination of variants in a gene may be called *2 (pronounced star two) while another combination may be called *3.

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Since we have two copies of each gene (one from our mother and one from our father) each person will have a combination of variants (haplotype) from each parent. When genetic testing is performed the results are noted as two numbers (one representing each combination of variants in that gene), separated by a slash. For example, someone who inherited the combination of variants from their mother known as *2 and the combination known as *3 from their father would be a *2/*3 for the gene tested. Some people have combinations of variants that are rare and have not been studied or named.

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The daughter has inherited the *1 haplotype from her mother and the *3 haplotype from her father. The son inherited the *2 haplotype from his mother and the *3 haplotype from his father.

Other Factors that Can Affect Response to Medication

How people respond to medications is not only determined by genetic variants they inherit from their parents. Age, sex, and weight factors can each influence how someone responds to a medication. In addition, diet and other drugs or supplements can affect drug response. For example, grapefruit and other citrus fruits, such as blood oranges, can interfere with how a person responds to certain medications, including anti-anxiety medications like BuSpar (buspirone) and cholesterol-lowering drugs like Lipitor® (atorvastatin).

Changing Your Medication

There are many factors your doctor takes into consideration when deciding which personalized medication to prescribe for you and at what dose. Only your healthcare provider can assess whether any changes should be made to your medication. Do not make any changes to your medication without talking with your doctor.

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A person’s predicted response to a drug, called a “metabolizer type,” is based on the haplotypes they inherited from their parents. “Metabolizer type” refers to how well a person can break down (or metabolize) the drug. This information can help determine how much benefit can be derived from taking the medication and what dosage may be the most effective. Based on someone’s metabolizer type, they may need a higher dose or lower dose of medication than normally prescribed.

The example to the right refers to the possible metabolizer types for the CYP2C19 gene, This gene contains the instructions for making an enzyme which is used to break down clopidogrel (as well as other drugs). Different haplotypes or combinations of variants on the CYP2C19 gene can be used to predict how a person may react to clopidogrel (Plavix®).

A genetic test is the first step to determining what personalized medicine is right for them. If you think pharmacogenetics is right for you, contact the Center for Medical Genetics today.

Page References
1. Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother 2008; 42(7):1017-25.
2. Lazarou, J, Pomeranz B, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA1998; 279: 1200-1205.

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