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What is Pharmacogenetics?

Pharmacogenomics (PGT or PGx) is the study of how genes affect a person’s response to drugs. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions.

PGT is a key feature in the emerging field of “precision medicine” which is rapidly changing healthcare.

Vision Laboratories aims to improve health outcomes, to lower the overall cost of healthcare, and, to increase patient engagement in their own healthcare by offering superior pharmacogenetic testing and reporting.

Vision Laboratories offers 19 clinically actionable pharmacogenetic biomarker tests

Our Comprehensive PGT reports cover over 33 drug classes associated with cancer treatment, cardiovascular health, diabetes, gastrointestinal health, infections, pain management, psychiatry, neurology, addiction, rheumatology, transplant surgery, and urology.

Reports simplify genomic data into intuitive support recommendations based on gravity and level of evidence. This information can help alert physicians to potential adverse events or lack of efficacy.

Available Biomarkers Tested

  • ANKK1/DRD2

    • Dopamine, a key neurotransmitter that controls cognition, emotion, locomotor activity, and other endocrine functions, exerts its action by binding to five different receptors, including the dopamine D2 receptor (DRD2). Dysregulation of dopaminergic signal transmission is found in many pathological conditions such as Parkinson’s disease and schizophrenia, and compounds that act as DRD2 agonists or antagonists are used to treat these conditions. Therapeutic and adverse events of several antipsychotics both result from their high affinity to antagonize DRD2.

  • APOE

    • Apolipoproteins (APO) are structural constituents of lipoprotein particles that have critical roles in blood lipid metabolism and transport. Apolipoprotein E (APOE) is a major constituent of triglyceride-rich chylomicrons, very low-density lipoproteins (VLDL), and some subclasses of high-density lipoproteins (HDL). The primary function of APOE is to transport cholesterol from the cells in the blood vessel wall to the liver for excretion. Defects in apolipoprotein E (APOE) can result in dyslipidemia, which is an important risk factor in the genesis of atherosclerosis and subsequent development of cardiovascular disease (CVD).

  • COMT

    • Catechol-O-Methyltransferase (COMT) is an enzyme responsible for the metabolism of catecholamines and catechol-estrogens in the central nervous system and other organs. Dopamine is cleared mainly by COMT in the frontal cortex, and a reduced activity of this enzyme results in higher synaptic levels of dopamine, which affects prefrontal cortex cognitive response to certain drugs. A single nucleotide polymorphism of the COMT gene produces an amino acid change from valine to methionine (Val158Met) and reduces the enzyme activity by 3- to 4-fold.

  • CYP1A2

    • The cytochrome P450 1A2 (CYP1A2) accounts for 13% of total CYP in the human liver, and is responsible for metabolizing 8-10% of commonly used drugs as well as natural compounds such as caffeine. A large inter-individual variability in the elimination of drugs that are metabolized by CYP1A2 has been observed, which has been ascribed to genetic variations and environmental factors. CYP1A2 activity is highly inducible (increased) by environmental factors including smoking (tobacco), some drugs, and several dietary compounds (cruciferous vegetables).

  • CYP2B6

    • The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of 4% of clinically important medications. This enzyme is highly polymorphic: to date, 37 different variants have been identified. The CYP2B6 assay identifies some common variants that are associated with variability in enzyme activity.

  • CYP2C19

    • The cytochrome P450 2C19 (CYP2C19) is involved in the metabolism of 10% of clinically important medications. This enzyme is highly polymorphic and more than 30 different alleles have been identified in various ethnicities. The CYP2C19 assay identifies common and rare variants that are associated with variability in CYP2C19 enzyme, which has important pharmacological and toxicological implications for antidepressants, benzodiazepines, antiplatelets, and proton-pump inhibitors.

  • CYP2C9

    • The cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of 15% of clinically important medications. This enzyme is highly polymorphic: to date, 30 variants have been identified. The CYP2C9 assay identifies some common variants that are associated with variability in CYP2C9 enzyme activity, which has important pharmacological and toxicological implications for anticonvulsants, anticoagulants, and certain antidiabetics.

  • CYP2D6

    • The cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 25% of clinically important medications. This enzyme is highly polymorphic: more than 100 different variants have been identified. The CYP2D6 assay identifies common variants that are associated with variability in CYP2D6 enzyme activity, which has important pharmacological and toxicological implications for antidepressants, antipsychotics, opioids, beta-blockers, and antiarrhythmics.

  • CYP3A4

    • The cytochrome P450 3A4 and 3A5 (CYP3A4 and CYP3A5) account for 40-80% of total CYP in human liver and intestine, respectively. Most importantly, CYP3A enzymes metabolize 50% of commonly used drugs. CYP3A4 and CYP3A5 enzymes have overlapping substrate specificity, and the contribution of CYP3A5 in the overall metabolism is smaller than the one for CYP3A4. The overall CYP3A metabolism status is expected to affect drugs that have a narrow therapeutic index.

  • CYP3A5

    • The cytochrome P450 3A4 and 3A5 (CYP3A4 and CYP3A5) account for 40-80% of total CYP in human liver and intestine, respectively. Most importantly, CYP3A enzymes metabolize 50% of commonly used drugs. CYP3A4 and CYP3A5 enzymes have overlapping substrate specificity, and the contribution of CYP3A5 in the overall metabolism is smaller than the one for CYP3A4. The overall CYP3A metabolism status is expected to affect drugs that have a narrow therapeutic index.

  • F2

    • Clotting Factor II, or prothrombin, is a vitamin K–dependent proenzyme that functions in the blood coagulation cascade. It is a precursor to thrombin, which converts fibrinogen into fibrin, which in turn strengthens a protective clot.

      The prothrombin 20210G>A mutation in the Factor II gene results in increased levels of plasma prothrombin and a concurrent increased risk for thrombosis. Prothrombin-related thrombophilia is characterized by venous thromboembolism (VTE). This risk of thrombosis is also increased when mutations exist for other coagulation factors such as Factor V Leiden, or in presence of non-genetic risk factors such as obesity, injury, surgery, smoking, pregnancy, use of estrogen-containing contraceptives, or replacement therapy. The clinical expression of Factor II thrombophilia is variable, and many individuals may never develop thrombosis, while others may experience venous thrombotic events or pregnancy complications.

  • F5

    • The Factor V gene encodes the coagulation Factor V. In normal conditions, Factor V is inactivated during the clotting process by the activated protein C (APC). In subjects with Factor V Leiden thrombophilia, a mutation in the gene produces a Factor V that cannot be inactivated normally by APC. As a result, the clotting process remains active longer than usual, leading to more thrombin generation. This hypercoagulable state is also increased when other mutations exist in other coagulation factors such as Factor II, or in the presence of non-genetic risk factors such as obesity, injury, surgery, smoking, pregnancy, or use of estrogen-containing contraceptive or estrogen containing replacement therapy. The clinical expression of Factor V Leiden thrombophilia is variable. Many individuals may never develop thrombosis, while others may experience venous thrombotic events or pregnancy complications. Certain circumstantial factors can increase the risk of thrombosis, and include: travel, central venous catheter use, pregnancy, oral contraceptive use, hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), organ transplantation, injury, age, and surgery. These factors are associated with the first thrombotic episode in at least 50% of individuals with a Factor V Leiden mutation.

  • ITGB3

    • The integrin beta 3 gene encodes the platelet glycoprotein IIIa (GBIIIa), which with other glycoproteins forms the integrin complex found on platelets (glycoprotein IIb/IIIa; GPIIb/IIIa). This integrin functions as a receptor for ligands such as fibrinogen and is critical for normal platelet aggregation and endothelial adherence. A polymorphism in the ITGB3 gene coding for the GBIIIa glycoprotein (176T>C, rs5918) results in a substitution of leucine to proline at position 59 of the GBIIIa subunit. This substitution is associated with increased platelet reactivity.

  • LPA

    • LPA is known as lipoprotein (a)or Apolipoprotein(a)and is a very large molecule. LPA is located at 6q25 locus. LPA encodes for a serine proteinase that inhibits activity of tissue type plasminogen activator. LPA forms a substantial portion of lipoprotein(a) and is proteolytically cleaved. The cleaved fragments of lipoprotein (a) attach to atherosclerotic lesions and promote thrombogenesis. Therefore elevated plasma levels of lipoprotein(a) are associated with increased risk of atherosclerosis and cardiovascular disease.

  • MTHFR

    • Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and is essential for the remethylation of homocysteine. Two common mutations in the MTHFR gene: 677C>T and 1298A> result in an enzyme with decreased activity, which is linked to increased plasma homocysteine levels (i.e., hyperhomocysteinemia). Mild to moderate hyperhomocysteinemia has been identified as a risk factor for venous thromboembolism and other cardiovascular diseases such as coronary heart disease and stroke. Other conditions in which hyperhomocysteinemia is found include recurrent pregnancy loss, placental infarction, and birth defects. However, the causal role of MTHFR mutations in these conditions is not well established.

  • OPRM1

    • “Mu” opioid receptors are the most important site of action of opioid drugs. Single polymorphisms in the human mu-opioid receptor (OPRM1)

      have been investigated for their role in human nociception, opiate efficacy, and addiction.

  • SLCO1B1

    • The SLCO1B1 gene encodes a liver-specific transporter involved in the removal of endogenous compounds (bile acids, bilirubin) and drugs such as statins from the blood to the liver. Some variants of the SLCO1B1 gene result in a low-functioning protein, which impairs statin clearance, and may lead to an increased risk of muscle pain, tenderness, or weakness, called myopathy. Certain medications can potently inhibit SLCO1B1, causing clinically significant drug interactions.

  • TPMT

    • The thiopurine S-methyltransferase (TPMT) is involved in the metabolism of thiopurine drugs, as well as other aromatic and heterocyclic sulfhydryl compounds. This enzyme is highly polymorphic: 28 variant alleles have been identified. The TPMT assay identifies important variants that are associated with variability in TPMT enzyme activity. TPMT activity is a significant predictor of serious adverse drug reactions

      (myelosuppression) in patients treated with thiopurine drugs.

  • VKORC1

    • The Vitamin K epoxide reductase complex, subunit 1 (VKORC1) is the target of anticoagulants. This enzyme is the rate-limiting step in the vitamin K cycle. Mutations in the VKORC1 gene results in variable expression levels of the VKORC1 enzyme and altered sensitivities towards anticoagulants. VKORC1 genotype defines three levels of clinical phenotype: high, moderate, and low sensitivity phenotypes towards warfarin (a widely used anticoagulant). Therefore, VKORC1 variant testing is usually used in conjunction with CYP2C9 variant testing to optimize warfarin dosing and minimize the risks of bleeding or thrombotic complications.