Pharmacogenomics involves the detection of genetic variations that contribute to the variability in drug effectiveness and toxicity that is observed between given individuals. These genetic differences in the metabolic pathways that affect the individual's response to various therapeutic drugs make it possible to individualize therapy.

Genetic differences between individuals can affect virtually all aspects of a disease and its treatment, including the rate of disease occurrence; the risk of disease progression or recurrence; the drug or drug class most likely to provide benefit; the therapeutic dose; the nature and extent of beneficial responses to treatment; and the likelihood of drug toxicity.

Drug Metabolism

The degree of drug effectiveness and some serious adverse drug reactions can be attributed to individual's unique genome and their ability to metabolize a given drug. Select individuals can produce enzymes that metabolize a drug more rapidly, for which the physician would prescribe a higher dosage to be effective. Conversely, other patients may require lower dosages for reduced enzyme activity. Sirona Dx Clinical Laboratories offers testing to proactively genotype patients which can allow the physician to prescribe a more effective drug at the most appropriate dosage without a long trial and error period. We currently offer tests that determine drug metabolizing genetic variants relevant to the most commonly prescribed drugs in the area of oncology.

Drug Side Effects

Millions of cases of adverse drug reactions (ADRs) are reported annually and account for thousands of deaths. This makes the ADRs one of the leading causes of hospitalization and death in the United States. Knowing the patient's genetic susceptibility to ADRs is instrumental in preventing adverse drug related consequences. An example of a genetic marker associated with ADR is HLA-B*5701 genotype and hypersensitivity to abacavir, used to treat HIV infection. Variants of the HLA genes are reported to be associated with adverse reactions with several therapeutic drugs. To mitigate potentially adverse drug reactions, the FDA recommends testing for HLA typing before administering such drugs. Sirona Dx Clinical Laboratories offers testing of a comprehensive battery of HLA biomarkers. The followings are examples of additional drugs associated with harmful reactions.

Clinical Utility:

  • Abacavir Hypersensitivity – HLA-B*57:01

    Abacavir is a nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. It is available under the trade name Ziagen and in two other formulations, Trizivir and Epzicom, both containing abacavir. Fatal hypersensitivity reactions have been associated with abacavir therapy. Symptoms include fever, skin rash, fatigue, nausea, vomiting, diarrhea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea or cough. Hypersensitivity is strongly associated with HLA-B*57:01, for which testing is now available in most countries. Screening for the HLA-B*57:01 has been convincingly shown to reduce the incidence of abacavir hypersensitivity reactions. Abacavir binds specifically to the peptide-binding groove of HLA-B*57:01 and thereby alters the spectrum of peptides that bind to this molecule. This leads to aberrant CD8 T-cell responses to self-antigens, which may explain the side effect.

    An FDA alert concerning abacavir and abacavir-containing medications was issued in July 2008 supporting pre-therapy screening for the presence of the HLA-B*57:01 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*57:01 are available and all patients should be screened for the HLA-B*57:01 allele before starting or restarting treatment with abacavir or abacavir containing medications. Development of clinically suspected abacavir hypersensitivity requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*57:01.

  • Allopurinol – HLA-B*58:01

    Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinol-induced SCAR.

  • Carbamazepine Hypersensitivity – HLA-A*31:01 & HLA-B*15:02

    Carbamazepine is an important treatment for seizure disorders, bipolar disorder, trigeminal neuralgia and chronic pain. However, carbamazepine is also associated with hypersensitivity reactions that range from benign urticaria to life-threatening cutaneous disorders, including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis. The latter two disorders carry a mortality that can be as high as 30% and require early diagnosis, with prompt withdrawal of all suspected potential causative drugs. The USA FDA has made a labeling change to the drug information for carbamazepine. Owing to recent data implicating the HLA allele HLA-A*31:01 and HLA-B*15:02 as markers for carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis, the FDA recommends genotyping for these alleles, particularly in populations with highest frequency of these alleles.


  • Phenytoin – HLA-B*15:02

    Phenytoin is a drug to treat epileptic seizures with a structural resemblance to carbamazepine, another antiepileptic drug. New studies have show when Asian patients who test positive for HLA-B*1502 are treated with phenytoin, they are at serious risks for developing adverse skin reactions. The occurrence of allele carriers with HLA-B*1502 is estimated to be 10-15% in patients from China, Thailand, Malaysia, Indonesia, the Philippines, and Taiwan.


Our Clinical Laboratories use a variety of techniques including Sanger Sequencing, Next Generation Sequencing, and Real-Time PCR to obtain the most reliable result.

Specimen Requirements:

One 5-mL EDTA (purple top) tube or 4 buccal swabs
Other anticoagulants accepted.

Shipping Requirements:

Samples are accepted Monday through Friday. Overnight shipments should be sent Monday through Thursday. Please send samples at room temperature.