The gene CYP2D6 has an extremely important role in drug metabolism. "Cytochrome P450, family 2, subfamily D, polypeptide 6" is the official name of CYP2D6. The gene is located at position 13.1 on the long (q) arm of chromosome 21 and encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that are heavily involved in drug metabolism (Genetics Home Reference, 2013), and many drugs are activated into their biologically active compounds. Because of numerous polymorphisms, the gene also has significant person-to-person variability. To date, more than 80 distinct CYP2D6 alleles and specific types and frequencies have been associated with different ethnic groups. CYP2D6*4 is the most common variant allele in Caucasians and, in that population, has a frequency of about 25%. On the other hand, CYP2D6*10 is common in the Asian population (Stearns & Rae, 2008).
References
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Desmarais, J.E., & Looper, K.J. (2009). Interactions between tamoxifen and anti-depressants via cytochrome P450 2D6. Journal of Clinical Psychiatry, 70, 1688-1697. doi:10.4088/JCP.08r04856blu
Goetz, M.P., Schaid, D.J., Wickerham, D.L., Safgren, S., Mushiroda, T., Kubo, M., … Ames, M.M. (2011). Evaluation of CYP2D6 and efficacy of tamoxifen and ralox-ifene in women treated for breast cancer chemoprevention: Results from the NSABP P1 and P2 clinical trials. Clinical Cancer Research, 17, 6944-6951. doi:10.1158/1078-0432.CCR-11-0860
Kaplan, M., & Mahon, S.M. (2013). Tamoxifen benefits and CYP2D6 testing in women with hormone receptor-positive breast cancer. Clinical Journal of Oncology Nursing, 17, 174-179. doi:10.1188/13.CJON.174-179
Madlensky, L., Natarajan, L., Tchu, S., Pu, M., Mortimer, J., Flatt, S., … Pierce, J. (2011). Tamoxifen metabolite concentrations, CYP2D6 genotype and breast cancer outcomes. Clinical Pharmacology and Therapeutics, 89, 718-725.
Regan, M.M., Leyland-Jones, B., Bouzyk, M., Pagani, O., Tang, W., Kammler, R., … Viale, G. (2012). CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: The Breast International Group 1-98 trial. Journal of the National Cancer Institute, 104, 441-451. doi:10.1093/jnci/djs125
Stearns, V., & Rae, J.M. (2008). Pharmacogenetics and breast cancer endocrine therapy: CYP2D6 as a predictive factor for tamoxifen metabolism and drug response? Expert Reviews in Molecular Medicine, 10(e34), 1-13.
