WHAT IS PHARMACOGENETIC TESTING?

Pharmacogenetic testing, also called DNA Drug Sensitivity Testing, is the testing of certain genes to determine how individuals might react to specific medications. With insight derived from pharmacogenetic testing, healthcare providers may decrease the need for “trial-and-error” dosing and might substantially reduce the risk Adverse Drug Events (ADEs).

Imperial Laboratories’ Pharmacogenetic Testing provides insight into a patient’s genetic propensity to experience a drug-to-drug interaction or to be non-responsive with certain medication classes.

This information is invaluable to clinicians whether they are initiating therapy or evaluating a patient’s progress. We evaluate 49 separate genes and over 120 variants to create an easy to understand report on 15 drug classes and 182 pharmacologic agents. This provides the clinician with one of the most robust reports in the industry and will help guide the clinician’s choices in pharmacotherapy.

COMMON QUESTIONS

Why is pharmacogenetics important?

When initiating drug therapy to treat a particular condition, healthcare practitioners typically prescribe one of several appropriate drugs. Dosages and timing of drugs are usually based upon the anticipated rate of metabolism and clearance from the body in the average person. They prescribe a “standard” dose based on factors such as weight, sex, and age. Clinically, however, each person responds uniquely to treatment and healthcare practitioners must make adjustments. For example, the healthcare practitioner may adjust the drug dose or switch to a different therapy, depending on whether the person’s condition is responding to the medication and whether the individual is experiencing unpleasant or dangerous side effects. Sometimes a person may find that a treatment that has been working well suddenly causes symptoms when that person starts taking an additional drug.

The concentrations or effects of some drugs are monitored with blood tests and the drug dosages may be increased or decreased to maintain the drug level in an established therapeutic range. Follow-up of drug concentration is called therapeutic drug monitoring. If changing the drug dose is not effective in treating or controlling the person’s condition, or the person still has side effects, then the person may be given a different drug.

In contrast, pharmacogenetics offers healthcare providers the opportunity to individualize drug therapy for people based on their genetic make-up. Testing people prior to initiating drug therapy to determine their likely response to different classes of drugs is a key emerging area of testing. Such genetic information could prove useful to both the healthcare practitioner and patient when choosing current and future drug therapies and drug doses. For certain medications, pharmacogenetics is already helping healthcare providers predetermine proper therapies and dosages to have a better chance of achieving the desired therapeutic effect while reducing the likelihood of adverse effects.

How do genes vary and how does pharmacogenetic testing work?

Genes are the basic units of genetic material, the segments of DNA that usually code for the production of specific proteins, including the proteins known as enzymes. Each person has two copies of most genes: one copy is inherited from the person’s mother and one copy is inherited from the person’s father. Each gene is made up of a specific genetic code, which is a sequence of nucleotides (A, T, G, or C). For each nucleotide position in the gene, one of the four nucleotides is the predominant nucleotide in the general population. This nucleotide is usually referred to as “wild type.” If an individual has a nucleotide that is different from “wild type” in one copy of his or her genes, that person is said to have a heterozygous variant. If an individual has the same variant nucleotide in both copies of his or her genes, that person is said to have a homozygous variant.

Nucleotide or genetic variants (also called polymorphisms or mutations) occur throughout the population. Some genetic variants are benign — do not produce any known negative effect or may be associated with features like height, hair color, and eye color. Other genetic variants may be known to cause specific diseases. Other variants may be associated with variable response to specific medications.

Pharmacogenetic tests look for genetic variants that are associated with variable response to specific medications. These variants occur in genes that code for drug-metabolizing enzymes, drug targets, or proteins involved in immune response. Pharmacogenetic tests have the ability to determine if a variant is heterozygous or homozygous, which can impact an individual’s response or reaction to a drug.

When are tests ordered?

A healthcare practitioner may test a patient’s genes for certain variations that are known to be involved in variable response to a medication at any time during treatment (for example, prior to treatment, during initial phase of treatment, or later in the treatment). The results of the testing may be combined with the individual’s clinical information, including age, weight, health and other drugs that they are taking, to help tailor therapy. Sometimes, the healthcare practitioner may use this information to adjust the medication dose or sometimes to choose a different drug. Pharmacogenetic testing is intended to give the healthcare practitioner additional information but may not replace the need for therapeutic drug monitoring.

Pharmacogenetic testing for a specific gene is only performed once since a person’s genetic makeup does not change over time. Depending on the medication, a single gene may be ordered or multiple genes may be ordered. An example of a medication for which multiple genes are usually evaluated is warfarin, which can be affected by genetic variation in CYP2C9 and VKORC1.

Testing may be ordered prior to starting specific drug therapies or if a person who has started taking a drug is experiencing side effects or having trouble establishing and/or maintaining a stable dose. Sometimes a person may not experience such issues until other medications that affect the metabolism or action of the drug in question are added or discontinued.

What are some examples of these tests?

Pharmacogenetic testing is available for a relatively limited number of drugs. Some tests may only be applicable to specific ethnic groups. The following are examples of some drugs for which pharmacogenetic tests are available:

Drug Associated Diseases/Conditions Gene(s) Tested
Warfarin (see Warfarin Sensitivity Testing) Excessive clotting disorder VKORC1 and CYP2C9
Thiopurines (azathioprine, mercaptopurine, and thioguanine) (see TPMT) Autoimmune/Childhood leukemia TPMT
Clopidogrel (see Clopidogrel (CYP2C19 Genotyping)) Cardiovascular CYP2C19
Irinotecan Cancer UGT1A1
Abacavir HIV HLA-B*5701
Carbamazepine, phenytoin Epilepsy HLA-B*1502
Some antidepressants, some antiepileptics (e.g., phenytoin, phenobarbital, carbamazepine, valproic acid) Psychiatric, Epilepsy CYP2D6, CYP2C9, CYP2C19, CYP1A2, SLC6A4,HTR2A/C
Tamoxifen Cancer CYP2D6
Some antipsychotics (e.g., haloperidol, mephobarbital, thioridazine) Psychiatric DRD3, CYP2D6, CYP2C19, CYP1A2
Methylphenidate Attention deficit disorder DRD4
Opioids Pain management OPRM1
5-fluorouracil Cancer DPYD variants and TYMS gene mutations testing
Selective serotonin reuptake inhibitors (SSRIs) Depression 5-HTT
Some statins (e.g., simvastatin) High cholesterol SLCO1B1

Should everyone have pharmacogenetic tests performed?

Currently they are only indicated if a person is going to take, or is taking, a drug that has an accepted pharmacogenetic test associated with it.