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This test provides genotypes for CYP3A4 and CYP3A5 and determines estimated metabolic activity. CYP3A4 and CYP3A5 cytochrome P450 enzymes are involved in the hepatic metabolism of up to 50% of all clinically used drugs. There is wide variation in enzyme activity, particularly for CYP3A4 (10-100 fold), due to both genetic and nongenetic factors. The cause of much of the variation is not yet understood.
This assay detects CYP3A4 alleles *1 and *22, and CYP3A5 alleles *1, *3, *6, *7. Other alleles are not detected by this assay. Metabolism of drugs may also be influenced by race, ethnicity, diet, and/or other medications. Results must be interpreted in the context of other test results and clinical findings. This test result does not rule out the possibility of variant alleles in other drug metabolism pathways that may affect drug efficacy and/or toxicity.
Multiplex polymerase chain reaction (PCR) and primer extension
The CYP3A4 and CYP3A5 enzymes have a high degree of similarity (85% amino acid sequence homology), and they metabolize largely the same set of drugs, though many use the CYP3A4 pathway predominantly. Genotype and metabolic activity for CYP3A4 and CYP3A5 should, therefore, be considered together when assessing possible effects on drug response. CYP3A4 *22 decreases enzyme activity and is present in approximately 8% of Caucasians. CYP3A5 *3 is a nonfunctional allele, so CYPA5 *3/*3 homozygotes are nonexpressors of CYP3A5. CYP3A5 *3 is the predominant CYP3A5 allele in Caucasians (prevalence of approximately 92%) and, therefore, most Caucasians have reduced or absent CYP3A5 metabolism. CYP3A5 *6 and *7 are also nonfunctional alleles with absent enzyme activity. CYP3A5 *6 and *7 are present in 11% to12% of Asians and African Americans, but are essentially absent in Caucasians (frequency of 0.1%). CYP3A4 *22 is typically associated with increased response to statins (lovastatin, simvastatin, and atorvastatin), with lower doses required to gain optimal response.
For CYP3A5, poor metabolizers are typically expected to require standard dosing of tacrolimus. Intermediate or extensive metabolizers are expected to require a higher starting dose of tacrolimus. Fentanyl is a key pain medication that is metabolized by CYP3A4/3A5. The CYP3A5 *3 variant has decreased clearance of this active drug. Patients with the CYP3A5 *3/*3 genotype have a higher risk of adverse events than patients with one or two *1 alleles; however, the CYP3A genotype and clinical variables (delivery rate, gender, comedications, kidney disease, BMI, and serum albumin) account for less than 50% of the wide variability in serum fentanyl concentration between patients with transdermal fentanyl treatment.
Whole blood or LabCorp buccal swab kit (The buccal swab collection kit contains instructions for the use of a buccal swab.)
7 mL whole blood or LabCorp buccal swab kit
3 mL whole blood or two buccal swabs
Maintain specimen at room temperature, or refrigerate at 4°C.
Causes for Rejection
Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; single buccal swab
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|504155||Cytochrome P450 3A4/3A5||81642-1||504161||3A4 Genotype:||81139-8|
|504155||Cytochrome P450 3A4/3A5||81642-1||504162||3A4 Metabolic Activity:||51971-0|
|504155||Cytochrome P450 3A4/3A5||81642-1||504163||3A5 Genotype:||81140-6|
|504155||Cytochrome P450 3A4/3A5||81642-1||504164||3A5 Metabolic Activity:||79717-5|
|504155||Cytochrome P450 3A4/3A5||81642-1||504165||Interpretation:||81146-3|
|504155||Cytochrome P450 3A4/3A5||81642-1||504166||Comments:||77202-0|
|504155||Cytochrome P450 3A4/3A5||81642-1||504167||CYP3A4/3A5 Information:||62364-5|
|504155||Cytochrome P450 3A4/3A5||81642-1||504168||References:||75608-0|
|504155||Cytochrome P450 3A4/3A5||81642-1||000000||Esoterix Informed Consent Req||N/A|