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 their mother and one copy is inherited from their father. Each gene is made up of a specific genetic code, which is a sequence of nucleotides. Each nucleotide can be one of four different 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 their genes, that person is said to have a heterozygous variant. If an individual has the same variant nucleotide in both copies of their 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 — they do not produce any known negative effect or may be associated with features like height, hair colour, and eye colour. 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 the immune response. Pharmacogenetic tests can determine if a variant is heterozygous or homozygous, which can affect an individual's response or reaction to a drug.
When are the tests requested?
A doctor may test a patient's genes for specific variations that are known to be involved in variable response to a drug at any time during treatment (for example, prior to treatment, during the 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 to the specific individual. Sometimes, the doctor may use this information to adjust the medication dose or sometimes to choose a different drug. Pharmacogenetic testing is intended to give the doctor 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 genes known as CYP2C9 and VKORC1.
Testing may be ordered prior to starting specific drug therapies or if someone who has started taking a drug is experiencing side effects or having trouble establishing and/or maintaining a stable dose. Sometimes patients may not experience such issues until other medications that affect the metabolism or action of the drug in question are added or discontinued.