Welcome to Healthscope Molecular
Pharmacogenomics explains how an individual’s genetic makeup affects the way they respond to specific medications. Recent advances in technology, now enables us to identify gene variants that can help predict possible adverse reactions or non-response in patients, prior to medication prescription.
Individual variation in response to drugs is a significant clinical problem. Such variation ranges from failure to respond to a drug, to adverse drug reactions and drug-drug interactions when several drugs are taken concomitantly. Inter-individual variability of drug response results from many factors, one being genetic.
It is anticipated that the use of pharmacogenomic testing will go some way to reduce the frequency of adverse drug reactions, while improving drug efficacy.
Healthscope Advanced Pathology now offers a range of genetic tests that may aid clinicians in selecting the appropriate treatment for their patients and avoid the “trial and error” form of prescribing.
Gene-drug and drug-drug interactions are interpreted and reported by a unique multidisciplinary approach. Personalised patient reports are prepared in conjunction with clinical geneticists and pharmacists at GenesFX Health.
Which patients will benefit from Pharmacogenomic testing?
- Those who experience adverse drug reactions to specific medication
- Non-responders to specific medication
- Those with a family history of medication problems
- Patients receiving multiple medications
- Potentially all patients prescribed medication
As well as the tests listed below the following individual genes are also available for genotyping: CYP2D6, CYP2C9, CYP2C19
DNAdose®
Healthscope Advanced Pathology, in conjunction with GenesFX Health now offers a premium pharmacogenomic service known as DNAdose - Personalised Prescribing.
Since many drugs are metabolized by multiple enzymatic pathways, DNAdose identifies gene variants in four major enzyme systems simultaneously. Together, these enzymes play an important role in metabolism and effect of more than 40% of commonly prescribed medications.
With the growing demand on clinicians to interpret DNA data, DNAdose now offers expert interpretation via a “Personalised Drug-specific Report” prepared by both clinical geneticists and pharmacists.
Genes Tested: CYP2D6, CYP2C9, CYP2C19 and VKORC1
Specimen Required: 4 mL whole blood in EDTA
Expected Results: 5-7 days
Medicare Rebate: No
Tamoxifen PredictAR
Tamoxifen can be considered a pro-drug that requires metabolism to elicit its pharmacological activity. Evidence now suggests that endoxifen, a secondary metabolite of tamoxifen, is most responsible for tamoxifen activity. In fact, endoxifen is 100 times more potent as an anti-estrogen than tamoxifen itself.
Cytochrome p450 2D6 (CYP2D6) is the main liver enzyme that metabolises tamoxifen to endoxifen. A number of commonly occurring gene variants have been identified in the CYP2D6 gene that significantly reduces the enzymes activity.
Approximately 10% of the Australian population has gene variants in their CYP2D6 gene that results in little or no enzyme activity. These individuals are known as poor metabolisers. As such, poor metabolisers may not receive the full medical benefit of tamoxifen therapy since they have little capacity to metabolise tamoxifen to endoxifen.
Tamoxifen PredictAR identifies common variants in the CYP2D6 gene that are responsible for an individual being a poor metaboliser.
Clopidogrel PredictAR
Clopidogrel is a widely used anti-platelet agent for the primary and secondary prevention of arterial thrombosis. Clopidogrel is administered as a pro-drug and is metabolized to its active metabolite by the hepatic cytochrome P450 2C19 (CYP2C19) enzyme. The active metabolite is responsible for the anti-platelet activity of clopidogrel.
Recent studies demonstrate that DNA variations in the gene for CYP2C19 result in significantly reduced production of the active metabolite of clopidogrel. Additional studies demonstrate that patients with variants in the CYP2C19 gene, including CYP2C19*2 &*3, have reduced production of the active metabolite of clopidogrel, reduced inhibition of platelet aggregation and increased incidence of coronary, cerebrovascular and coronary stent thrombosis.
Clopidogrel PredictAR identifies common variants in the CYP2C19 gene.
Advantages of Genotyping in Predicting Response to Clopidogrel Treatment
- By establishing the CYP2C19 genotype the clinician can now accurately predict if clopidogrel treatment is likely to be effective in the patient requiring anti-platelet therapy.
- In patients currently receiving clopidogrel treatment and in whom a concern exists regarding the potential anti-thrombotic efficacy of this agent determination of CYP2C19 genotype will assist in determining the likely anti-thrombotic benefit of established clopidogrel treatment.
Specimen Required: 4 mL whole blood in EDTA
Expected Results: 5-7 days
Medicare Rebate: No
TPMT PredictAR
TPMT PredictAR determines an individual’s thiopurine methyltransferase (TPMT) genotype. TPMT is the primary enzyme responsible for thiopurine drug based metabolism. Thiopurine drugs (azathioprine, 6-mercaptopurine and 6-thioguanine) require conversion to thioguanine nucleotides to exert their therapeutic (cytotoxic) effect, however that conversion can be blocked by methylation or oxidation. The methylation pathway depends on TPMT activity.
TPMT activity is significantly affected by a common genetic polymorphism found in the TPMT gene. Approximately 89% of the population have high enzyme activity and are homozygous for the normal allele, 11% inherit intermediate levels of enzyme activity with one normal and one variant allele, while 1 in 300 have no functional activity (two variant alleles, homozygous TPMT).
Thioguanine nucleotides can accumulate in patients who have reduced TPMT activity and who are receiving standard thiopurine doses, which may then lead to severe and possibly fatal myelosuppression.
Benefits and Clinical Use of TPMT PredictAR
- TPMT genotyping makes it possible to accurately identify patients who are at high risk of thiopurine drug toxicity.
- A patient’s genotype does not change, so it only needs to be determined once.
- Methods for measuring red blood cell (RBC) TPMT activity are available, but results may be falsely elevated by recent blood transfusions. TPMT genotype testing can predict reduced TPMT activity and is not affected by these variables.
Specimen Required: 4 mL whole blood in EDTA
Expected Results: 5-7 days
Medicare Rebate: No
Warfarin PredictAR
Warfarin therapy can be difficult to manage because of the drug’s narrow therapeutic index and the wide inter-individual variability in patient response. It is now clear that much of this variability is largely genetically determined. Two common genetic variants in the CYP2C9 gene (CYP2C9*2 and CYP2C9*3) are associated with impaired metabolism of warfarin, while variants in the gene for vitamin K epoxide reductase complex 1 (VKORC1) correlate with warfarin sensitivity and resistance.
By combining patient clinical characteristics with knowledge of CYP2C9 and VKORC1 genotypes, as much as 60% of the variability in warfarin dose requirements can be explained.
Genotyping patients prior to, or shortly after, commencing warfarin could improve achievement of a stable INR and potentially reduce the rate of early bleeding.
Advantages of genotyping in predicting warfarin maintenance doses
- A clinician can now more accurately determine the warfarin induction and maintenance dosage, thereby minimising possible adverse reactions such as excessive bleeding or harmful clot formation.
- Warfarin therapeutic steady state level can be reached more quickly, thereby reducing the period of trial and error.
Specimen Required: 4 mL whole blood in EDTA
Expected Results: 3-5 days
Medicare Rebate: No
Irinotecan PredictAR
Irinotecan PredictAR detects the presence of the UGT1A1*28 allele.
In July 2005, the FDA approved revisions to the safety labeling for Irinotecan-HCl injection to recommend reduced dosing in patients who are homozygous for the UDP-glucuronosyltransferase 1A1 (UGT1A1)-*28 allele.
UGT1A1 conjugates the active metabolite of irinotecan, S-38 to a glucuronide metabolite. Its activity is reduced in patients with the variant allele UGT1A1*28. Homozygosity of this allele is found in 10% of the population.
Specimen Required: 4 mL whole blood in EDTA
Expected Results: 3-5 days
Medicare Rebate: No