| Cytochrome P450 2D6 (CYP2D6) is a member of the CYP450 enzyme superfamily that is extensively involved in drug metabolism including selective serotonin reuptake inhibitors, tricyclic antidepressants, and beta-blockers, among many others. CYP2D6 is also involved in the metabolism of Tamoxifen, a selective estrogen receptor modulator used to treat and prevent recurrence in breast cancer. Nucleotide variations producing either decreased or increased enzyme activities have been identified in the CYP2D6 gene. Individuals with two copies of the non-functional alleles (Poor Metabolizers) have inactive CYP2D6 activity, resulting in either adverse drug reactions or decreased drug efficacy. Individuals with increased copy number of the CYP2D6 gene (Ultra rapid Metabolizers) have higher than normal enzyme activity and may require increased doses to achieve therapeutic response. About 7-10% of Caucasians are CYP2D6 poor metabolizers. The following are examples of pharmaceutical agents that may be affected by CYP2D6 genotype. 1. Agents to treat depression: These include the class of drugs known as selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants. Individuals who have two copies of inactivating 2D6 variations are referred to as poor metabolizers. These individuals may require lower than usual doses to achieve safety and efficacy. Individuals who have two copies of variations resulting in increased activity are referred to as ultra-rapid metabolizers who may need increased drug dosages. 2. Tamoxifen: Tamoxifen is a selective estrogen receptor modulator that binds to the estrogen receptor and is used in the treatment of estrogen-receptor positive breast cancer. Tamoxifen is metabolized by CYP2D6 to an active form that has much higher affinity for the estrogen receptor than does Tamoxifen. Individuals who are CYP2D6 poor metabolizers and are taking Tamoxifen may have decreased levels of the active metabolite and thus may have decreased efficacy of the drug and a higher frequency of breast cancer relapse. Increasing the dose of Tamoxifen in poor metabolizer patients does not appear to improve outcomes for this group of patients. This analysis tests 16 different variants associated with altered CYP2D6 activity. Reasons For Referral:
Limitations:
Testing Methodology:
This analysis incorporates DNA amplification by multiplex PCR, allele specific primer extension, microarray hybridization and Fluorescence signal detection.
Analytical Sensitivity and Specificity:Greater than 99% Specimen Requirements:Blood: EDTA (purple-top) tubes: Adults: 3cc.
Turnaround Time:2 weeks CPT Codes and Prices:Index: 83891, 83900, 83901x2, 83914x29, 83912 Shipping InformationForms:References:
Test Codes:Index: 6875 |