What Is Pharmacogenetics Testing?

Pharmacogenetic testing provides information about genes that encode the cytochrome P450 (CYP450) enzymes, which help the body metabolize drugs. Genetic variations (polymorphisms) can alter the activity of these enzymes from one person to another. As a result, the same drug may affect one person differently from another. Results of pharmacogenetic testing can examine these variations and predict how your body uses different medications. This information can be used by your healthcare provider to recommend medications.

An example of a CYP450 enzyme is CYP2D6, which is involved in the body's processing of several medications, including codeine. More than 100 variations of CYP2D6 have been identified that affect its activity. For example, some individuals have high CYP2D6 enzyme activity and break down codeine so quickly that a standard dose can cause dangerous side effects. Some people have decreased CYP2D6 enzyme activity and can't activate codeine, so they don't get pain relief from codeine. Other individuals have normal CYP2D6 enzyme activity and can process the medication normally. If pharmacogenomic testing shows the person doesn't respond well to codeine, a different medication may need to be prescribed.

A common CYP450 enzyme is CYP2C19, which breaks down medications such as citalopram and escitalopram. Additionally, this enzyme has many known variations that affect its activity. In people with decreased CYP2C19 activity, citalopram prescribed for depression or anxiety cannot be effectively metabolized. This may result in a buildup of medication in the body and a higher risk of side effects. It may be necessary to modify the dosage or change the medication.

Besides genetic differences, environmental factors could also affect a person's response to medication. Each medication has its characteristics. In the examples above, a decreased breakdown of codeine can lead to a lack of effect of the medication. By contrast, a decreased breakdown of citalopram can result in side effects. Moreover, drug interactions can affect the way a person responds to the medication. People who take medications that inhibit CYP2D6 will be unable to break down codeine effectively.

Medications that may be affected by genetic differences include:

• Ziagen (abacavir) treats HIV infection. A genetic variation in the HLA-B gene can cause severe skin reactions.
• Herceptin (trastuzumab) is used to treat breast cancer. It can only be prescribed to women with a genetic makeup that produces more of the protein HER2.
• Elitek (rasburicase) is used to treat hyperuricemia in people with cancer. Those who do not carry normal functioning G6PD enzymes are at a high risk of having too many red blood cells destroyed by the body.
• Imuran (azathioprine) is an immunosuppressant. There is a possibility that changes in the proteins TPMT and NUDT15 can affect how the drug is broken down, resulting in the suppression of bone marrow activity.
• Prograf (tacrolimus) is used for organ transplants. Drug metabolism may be affected by changes in CYP3A5. Rapid breakdown of the drug can lead to the transplanted organ being rejected.
• Zyloprim (allopurinol) is used to treat gout. In people taking allopurinol, a single genetic variation in the HLA-B gene can cause a painful skin reaction.
• Plavix (clopidogrel) is used for antiplatelet treatment. Your liver's CYP2C19 enzyme can affect how much clopidogrel is active in your body. It could lead to the drug not working in your body.

When a medicine doesn't work well or causes side effects, doctors might order pharmacogenetic testing before starting it or changing it.

Using pharmacogenetic testing, doctors can pick certain medicines for the following:

• Acid reflux
• Anxiety
• Cancer
• Depression
• Heart disease
• Infections
• Pain
• Seizures

Tests are also useful when a person's immune system needs to be suppressed (blocked or turned down) after an organ transplant because the immune system won't recognize the donor organ and can attack it. The right dose of immune-blocking medicine can help protect the new organ and the person's health.

Pharmacogenetic studies report how genes influence how a person's body responds to medications.

The selection of medication and dose is usually based on a "one-size-fits-all" model. In addition to determining eye and hair color, genes may also influence how people break down medications. Some people may experience side effects, whereas others may not feel therapeutic benefits despite taking the same medication at the same dose.

Other factors, such as age, lifestyle, and drug-drug interactions, can also affect your medication response. Healthcare providers consider these factors when providing care, but pharmacogenomics can help them personalize treatments according to your genetic makeup. If possible, try to avoid changing any medication without first consulting your physician.

Genes can influence the response to medicine in several ways, and pharmacogenomics can navigate healthcare providers by understanding how your body responds to different drugs.

• What the body does when it metabolizes (breaks down) and removes medications. Medicines are not broken down in the same way by every individual's body. The breakdown of medicines may be too fast or too slow for some people. Some medicines break down too quickly, so the level of the drug in a person's body may be too low for it to work properly. Those that break down too slowly can cause too many drugs in the body, causing side effects.
• Medicines are activated by the body. The body must activate or switch some medicines for them to work. In the case of too much active medicine being turned on by the body, side effects can occur. When the body does not get enough medicine, it might not work.
• What are the chances of someone having a severe reaction to a medicine. Genes can increase a person's risk of a rare but serious reaction to medicine. In cases where someone has one of these genes, doctors can prescribe safer medicines.

Many benefits can be gained from the use of pharmacogenetics, including:

• Avoid drugs that may not be effective or may cause unwanted side effects.
• Safer prescriptions because a physician can predict what drugs and dosages a person will respond to, resulting in fewer side effects for the person.
• The development of new and more effective drugs for treating conditions such as pain, nausea, and heart disease.

Along with improving the way existing drugs are used, genome research will lead to the development of better drugs. New drugs should be highly effective and not cause serious side effects.

In the past, drug developers typically chose chemicals that had broad action against the disease. Scientists are now using genomic information to find or design drugs for specific subgroups of people. Researchers are using pharmacogenetic tools to identify drugs that target specific molecular and cellular pathways.

The field of pharmacogenomics may allow drug development to restart for some drugs that were abandoned during development. Several beta-blocker drugs have been approved for treating heart failure, including Gencaro (bucindolol). Gencaro's interest was revived after tests showed it worked well in people with two genetic variants that control heart function. Gencaro could become the first prescription heart drug to require genetic testing before prescription if approved by the FDA.

Most drugs are prescribed based on the person's age, weight, sex, and liver and kidney function. Researchers have identified gene variants that affect how people respond to a few drugs. For each person, doctors can choose the right medication and dose.

Along with learning how people respond to medications, pharmacogenetics can be helpful to discern the types of diseases that people suffer from.

Pharmacogenetic testing may help narrow the number of medications to try, but it cannot pinpoint the "most appropriate" medication for you. Testing does not provide information about the response to all medications prescribed in the United States nor about the effect of dietary and herbal supplements.