Cytochrome P450 3A4 (CYP3A4) Genotyping

Test Code

CPT Code

Whole blood or buccal swabs

5 mL of whole blood or four buccal swabs

Minimum Volume
3 mL of whole blood or four buccal swabs

Lavender-stopper (EDTA) tube or paper envelope for dried buccal swabs

Storage Instructions
Maintain at room temperature or refrigerate

Cause for Rejection
Hemolyzed specimen; quantity not sufficient

General Purpose and Use
CYP3A4 is a liver enzyme that, in concert with CYP3A5, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A4 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A4 substrates. Roughly 4-10% of the general population possesses inherited differences in 3A4 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A4.

Alleles Detected:
Active alleles: CYP3A4*1
Inactive alleles: CYP3A4*3, *17, *22

Phenotype Categories

  • Extensive metabolizers (EM) represent the norm for metabolic capacity. Genotypes consistent with the EM phenotype include two active CYP3A4 alleles.
  • Partially decreased metabolizers (PDM) represent reduced metabolic capacity.  Genotypes consistent with the PDM phenotype are those with one active and one inactive CYP3A4 allele.
  • Decreased metabolizers (DM) are at increased risk of drug-induced side effects due to diminished drug elimination or lack of therapeutic effect resulting from failure to generate the active form of the drug. Genotypes consistent with the PM phenotype are those with no active CYP3A4 alleles.

Other variants of the CYP3A4 gene that are not detected in this assay may influence drug metabolism.  CYP3A4 metabolic capacity is also influenced by concomitant medications, inhibitors, inducers, diet and various disease states.  All factors should be considered as part of the overall patient management strategy.

Real-time polymerase chain reaction with fluorescence detection.

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