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Genetic variations associated with drug response or drug disposition may predispose a patient to risk of drug-related toxicity or lack of therapeutic benefit and are referred to as pharmacogenetic variants. Pharmacogenetics can explain and predict variations in both pharmacokinetic and pharmacodynamic processes.
As such, pretherapeutic pharmacogenetic testing to identify people who have inherited clinically significant variants may guide drug and dose selection to promote personalized therapeutics. Pharmacogenetic testing may be designed to detect human germ-line variants, somatic variants (eg, tumor tissue), or genomic variants of an infectious organism (eg, virus). The goals of pharmacogenetic testing are to reduce the high number of nonresponders (averaging 30-60% of patients) and to reduce adverse drug reactions.
Tests generally appear in the order most useful for common clinical situations
| Test name: 5-Fluorouracil (5-FU) Toxicity and Chemotherapeutic Response, 7 Mutations |
| ARUP #: 2007228 |
| Methodology: Polymerase Chain Reaction/Single Nucleotide Extensions/Fragment Analysis |
| Use: Use to detect genetic variants that influence metabolism of 5-FU Only the targeted DPYD and TYMS mutations will be evaluated |
| Limitations: Genotype should be interpreted with clinical information; consultation with clinical pharmacist recommended Rare diagnostic errors can occur due to primer-site mutations |
| Test name: HLA-B*5701 Associated Variant Genotyping for Abacavir Sensitivity |
| ARUP #: 2002429 |
| Methodology: Polymerase Chain Reaction/Fluorescence Monitoring |
| Use: Standard of care prior to abacavir therapy per FDA Screening test to determine susceptibility to abacavir hypersensitivity syndrome |
| Limitations: Routinely used in many countries before introducing patient to abacavir Less predictive of hypersensitivity within black population Frequency of HLA-B*5701 is very low in Asian populations, limiting value of test in this population 80-fold increase in liver injury risk for patients on flucloxacillin |
| Test name: Cytochrome P450 2C9 (CYP2C9) 2 Mutations |
| ARUP #: 0051103 |
| Methodology: Polymerase Chain Reaction/DNA Hybridization/Electrochemical Detection |
| Use: Aids in warfarin dosage planning in conjunction with VKORC1 testing Most useful for
Other uses
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| Limitations: Does not provide individualized dosing recommendations Additional mutations in this or other genes will not be detected Mutation detection is not a substitute for therapeutic drug or other clinical monitoring Nongenetic factors may also affect drug metabolism |
| Follow-up: Refer to Warfarin Genotyping Plus test if individualized warfarin dosing recommendations are needed |
| Test name: Warfarin Genotyping Plus |
| ARUP #: 2004358 |
| Methodology: Polymerase Chain Reaction/DNA Hybridization/Electrochemical Detection |
| Use: This is the preferred test for warfarin dosage planning Warfarin Sensitivity (CYP2C9 and VKORC1) 3 Mutations test is performed and individualized dosing recommendations are provided when specific patient parameters are submitted Clinical utility has not been established |
| Test name: Warfarin Sensitivity (CYP2C9 and VKORC1 ) 3 Mutations |
| ARUP #: 0051370 |
| Methodology: Polymerase Chain Reaction/DNA Hybridization/Electrochemical Detection |
| Use: Aids in warfarin dosage planning Most useful for
Does not provide individualized dosing recommendations Clinical sensitivity - 90% of CYP2C9 and VKORC1 mutations causing warfarin sensitivity in Caucasians are detected; the detection rate in other ethnicities is reduced |
| Limitations: Other mutations that may impact warfarin sensitivity or resistance in these genes or other genes will not be detected Rare mutations within primer or probe regions may interfere with the assay |
| Follow-up: Refer to Warfarin Genotyping Plus test if individualized warfarin dosing recommendations are needed |
| Test name: Cytochrome P450 2D6 (CYP2D6) 14 Mutations and Gene Duplication |
| ARUP #: 0051232 |
| Methodology: Polymerase Chain Reaction/Primer Extension |
| Use: Order to detect CYP2D6 allelic variants associated with impaired or increased drug metabolism May aid in dose planning for drugs such as
|
| Limitations: Only the targeted CYP2D6 mutations will be detected; mutations in other genes will not be detected Additional mutations in this or other genes will not be detected Mutation detection is not a substitute for therapeutic drug or other clinical monitoring Nongenetic factors may also affect drug metabolism |
| Test name: Cytochrome P450 2C19 (CYP2C19) 9 Mutations |
| ARUP #: 0051104 |
| Methodology: Polymerase Chain Reaction/Primer Extension |
| Use: Order to detect CYP2C19 allelic variants associated with impaired (*2, *3) or increased (*17) drug metabolism May aid in dose planning for drugs such as
|
| Limitations: Additional mutations in this or other genes will not be detected Mutation detection is not a substitute for therapeutic drug or other clinical monitoring Nongenetic factors may also affect drug metabolism |
| Test name: KRAS Mutation Detection |
| ARUP #: 0040248 |
| Methodology: Polymerase Chain Reaction/Pyrosequencing |
| Use: Order to assess resistance to anti-EGFR therapy (cetuximab and panitumumab) |
| Limitations: 40% of wild-type, KRAS-type tumors will not respond to anti-EGFR monoclonal antibodies |
| Test name: KRAS Mutation Detection with Reflex to BRAF Codon 600 Mutation Detection |
| ARUP #: 2001932 |
| Methodology: Polymerase Chain Reaction/Pyrosequencing |
| Use: Order to assess response to EGFR-directed therapy Detects mutations in codons 12, 13, and 61; if KRAS is not detected, BRAF codon 600 Mutation Detection will be performed |
| Test name: NRAS Mutation Detection by Pyrosequencing |
| ARUP #: 2003123 |
| Methodology: Polymerase Chain Reaction/Pyrosequencing |
| Use: Order to predict response to EGFR-directed therapy |
| Test name: UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping |
| ARUP #: 0051332 |
| Methodology: Polymerase Chain Reaction/Fragment Analysis |
| Use: May be useful for dose planning in individuals who
May be used to diagnose suspected Gilbert syndrome (benign familial hyperbilirubinemia) |
| Limitations: No specific dosing recommendations are available for patients with decreased UGTIAI activity Clinical significance of the rare (TA)5 and (TA)8 alleles in predicting irinotecan toxicities is not well established; genetic and nongenetic factors other than UGT1A1 may contribute to irinotecan toxicity and efficacy |
| Test name: Pseudocholinesterase, Dibucaine Inhibition |
| ARUP #: 0020159 |
| Methodology: Quantitative Enzymatic |
| Use: Order to detect increased sensitivity in individuals who experience prolonged paralysis following succinylcholine or mivacurium administration |
| Test name: Mercaptopurine Quantitation, Serum or Plasma |
| ARUP #: 0091084 |
| Methodology: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Compliance monitoring |
| Test name: Thiopurine Methyltransferase, RBC |
| ARUP #: 0092066 |
| Methodology: Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry |
| Use: Preferred screening test to detect individuals at excess risk for myelosuppression when exposed to standard dose of thiopurines May aid in dose planning for individuals who will receive thiopurine drugs Intended for pretherapeutic evaluation only |
| Limitations: Do not use for patients currently on thiopurine (will give falsely low results) or who have had a blood transfusion in the last 30 days |
| Test name: EGFR Mutation Detection by Pyrosequencing |
| ARUP #: 2002440 |
| Methodology: Polymerase Chain Reaction/Pyrosequencing |
| Use: Order to assess response to gefitinib therapy for non-small cell lung cancer Detects mutations in EGFR exons 18, 19, 20, and 21 |
| Test name: TPMT Genotype |
| ARUP #: 2002573 |
| Methodology: Qualitative Polymerase Chain Reaction |
| Use: Aids in detecting individuals at high risk for myelosuppression when exposed to standard dose of thiopurines Consider if red blood cell (RBC) TPMT testing is not practical, as in the following
|
| Limitations: TPMT polymorphism explains only 60% of the thiopurine hematotoxicity but none of the thiopurine induced liver injury Continued monitoring on hematologic and liver parameters is necessary |
| Test name: Thiopurine Metabolites |
| ARUP #: 2002575 |
| Methodology: Qualitative High Pressure Liquid Chromatography (High Performance Liquid Chromatography) |
| Use: Aids in therapeutic monitoring in individuals treated with thiopurines |
| Test name: Interleukin 28 B (IL28B)-Associated Variants, 2 SNPs |
| ARUP #: 2004680 |
| Methodology: Qualitative Polymerase Chain Reaction/Qualitative Fluorescence Monitoring |
| Use: Detects genetic variants associated with interleukin 28 B (IL28B) that predict
|
| Limitations: SNPs other than those targeted will not be detected |
| Test name: Inosine Triphosphatase (ITPA) and Interleukin 28 B (IL28B)-Associated Variants, 4 SNPs |
| ARUP #: 2006344 |
| Methodology: Polymerase Chain Reaction/Single Nucleotide Extensions |
| Use: Detect genetic variants associated with interleukin 28 B (IL28B) that may aid in
Detect genetic variants associated with inosine triphosphatase (ITPA) that may aid in
|
| Limitations: SNPs other than those targeted will not be detected |
| Test name: Warfarin, Urine |
| ARUP #: 0091230 |
| Methodology: High Performance Liquid Chromatography |
| Comments: |
| Test name: Warfarin, Serum or Plasma |
| ARUP #: 0090805 |
| Methodology: High Performance Liquid Chromatography |
| Comments: |
| Test name: Pseudocholinesterase, Total |
| ARUP #: 0020167 |
| Methodology: Quantitative Enzymatic |
| Comments: |