Complexities of CYP2D6 gene analysis and interpretation

References

• Abduljalil, K., Frank, D., Gaedigk, A., Klaassen, T., Tomalik-Scharte, D., Jetter, A., … Fuhr, U. (2010). Assessment of activity levels for CYP2D6*1, CYP2D6*2, and CYP2D6*41 genes by population pharmacokinetics of dextromethorphan. Clinical Pharmacology and Therapeutics, 88, 643–651.
   PubMed Web of Science ®Google Scholar
• Aklillu, E., Persson, I., Bertilsson, L., Johansson, I., Rodrigues, F. & Ingelman-Sundberg, M. (1996). Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. Journal of Pharmacology and Experimental Therapeutics, 278, 441–446.
   PubMed Web of Science ®Google Scholar
• Bertilsson, L., Dahl, M.L., Dalén, P. & Al-Shurbaji, A. (2002). Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs. British Journal of Clnical Pharmacology, 53, 111–122.
   PubMed Web of Science ®Google Scholar
• Black, J.L., Walker, D.L., O’Kane, D.J. & Harmandayan, M. (2011). Frequency of undetected CYP2D6 hybrid genes in clinical samples: Impact on phenotype prediction. Drug Metabolism and Disposition, 40, 111–119.
   PubMedGoogle Scholar
• Blake, M.J., Gaedigk, A., Pearce, R.E., Bomgaars, L.R., Christensen, M.L., Stowe, C., … Leeder, J.S. (2007). Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clinical Pharmacology and Therapeutics, 81, 510–516.
   PubMed Web of Science ®Google Scholar
• Borges, S., Desta, Z., Jin, Y., Faouzi, A., Robarge, J.D., Philips, S., … Li, L. (2010). Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patients. Journal of Clinical Pharmacology, 50, 450–458.
   PubMed Web of Science ®Google Scholar
• Borges, S., Desta, Z., Li, L., Skaar, T. C., Ward, B. A., Nguyen, A., … Flockhart, D. A. (2006). Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: Implication for optimization of breast cancer treatment. Clinical Pharmacology and Therapeutics, 80, 61–74.
   PubMed Web of Science ®Google Scholar
• Brauch, H., Schroth, W., Goetz, M.P., Murdter, T.E., Winter, S., Ingle, J.N., … Eichelbaum, M. (2013). Tamoxifen use in postmenopausal breast cancer: CYP2D6 matters. Journal of Clinical Oncology, 31, 176–180.
   PubMed Web of Science ®Google Scholar
• Chida, M., Ariyoshi, N., Yokoi, T., Nemoto, N., Inaba, M., Kinoshita, M. & Kamataki, T. (2002). New allelic arrangement CYP2D6*36 x 2 found in a Japanese poor metabolizer of debrisoquine. Pharmacogenetics, 12, 559–562.
   PubMedGoogle Scholar
• Chladek, J., Zimova, G., Beranek, M. & Martinkova, J. (2000). In-vivo indices of CYP2D6 activity: Comparison of dextromethorphan metabolic ratios in 4-h urine and 3-h plasma. European Journal of Clinical Pharmacology, 56, 651–657.
   PubMed Web of Science ®Google Scholar
• Cohen, J., Wilson, A. & Manzolillo, K. (2012). Clinical and economic challenges facing pharmacogenomics. Pharmacogenomics Journal, 13, 378–388.
   PubMed Web of Science ®Google Scholar
• Contreras, A.V., Monge-Cazares, T., Alfaro-Ruiz, L., Hernandez-Morales, S., Miranda-Ortiz, H., Carrillo-Sanchez, K., … Silva-Zolezzi, I. (2011). Resequencing, haplotype construction and identification of novel variants of CYP2D6 in Mexican Mestizos. Pharmacogenomics, 12, 745–756.
   PubMed Web of Science ®Google Scholar
• Cornetta, K. & Brown, C.G. (2013). Balancing personalized medicine and personalized care. Academic Medicine, 88, 309–313.
   Google Scholar
• Crews, K.R., Cross, S.J., McCormick, J.N., Baker, D.K., Molinelli, A.R., Mullins, R., … Hoffman, J.M. (2011). Development and implementation of a pharmacist-managed clinical pharmacogenetics service. American Journal of Health-System Pharmacy, 68, 143–150.
   PubMed Web of Science ®Google Scholar
• Crews, K.R., Gaedigk, A., Dunnenberger, H.M., Klein, T.E., Shen, D.D., Callaghan, J.T., … Skaar, T.C. (2012). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clinical Pharmacology & Therapeutics, 91, 321–326.
   PubMed Web of Science ®Google Scholar
• Crews, K.R., Hicks, J.K., Pui, C.H., Relling, M.V. & Evans, W.E. (2012). Pharmacogenomics and individualized medicine: Translating science into practice. Clinical Pharmacology and Therapeutics, 92, 467–475.
   PubMed Web of Science ®Google Scholar
• Crisafulli, C., Fabbri, C., Porcelli, S., Drago, A., Spina, E., De Ronchi, D. & Serretti, A. (2011). Pharmacogenetics of antidepressants. Frontiers in Pharmacology, 2, 60. eCollection.
   PubMedGoogle Scholar
• Dahl, M.L., Johansson, I., Bertilsson, L., Ingelman-Sundberg, M. & Sjoqvist, F. (1995). Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. Journal of Pharmacology and Experimental Therapeutics, 274, 516–520.
   PubMed Web of Science ®Google Scholar
• Dalén, P., Dahl, M.L., Bernal Ruiz, M.L., Nordin, J. & Bertilsson, L. (1998). 10-hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clinical Pharmacology & Therapeutics, 63, 444–451.
   PubMed Web of Science ®Google Scholar
• Daly, A.K., Brockmöller, J., Broly, F., Eichelbaum, M., Evans, W.E., Gonzalez, F.J., … Zanger, U.M. (1996). Nomenclature for human CYP2D6 alleles. Pharmacogenetics, 6, 193–201.
   PubMedGoogle Scholar
• Daly, A.K., Fairbrother, K.S., Andreassen, O.A., London, S.J., Idle, J.R. & Steen, V.M. (1996). Characterization and PCR-based detection of two different hybrid CYP2D7P/CYP2D6 alleles associated with the poor metabolizer phenotype. Pharmacogenetics, 6, 319–328.
   PubMedGoogle Scholar
• Di Francia, R., Valente, D., Catapano, O., Rupolo, M., Tirelli, U. & Berretta, M. (2012). Knowledge and skills needs for health professions about pharmacogenomics testing field. European Review for Medical and Pharmacological Sciences, 16, 781–788.
   PubMed Web of Science ®Google Scholar
• Dodgen, T.M., Hochfeld, W.E., Fickl, H., Asfaha, S.M., Durandt, C., Rheeder, P., … Pepper, M.S. (2013). Introduction of the AmpliChip CYP450 test to a South African cohort: A platform comparative prospective cohort study. BMC Medical Genetics, 14, 20.
   PubMedGoogle Scholar
• Dunbar, L., Butler, R., Wheeler, A., Pulford, J., Miles, W. & Sheridan, J. (2012). Clinician experiences of employing the AmpliChip® CYP450 test in routine psychiatric practice. Journal of Psychopharmacology, 26, 390–397.
   PubMedGoogle Scholar
• Ebisawa, A., Hiratsuka, M., Sakuyama, K., Konno, Y., Sasaki, T. & Mizugaki, M. (2005). Two novel single nucleotide polymorphisms (SNPs) of the CYP2D6 gene in Japanese individuals. Drug Metabolism and Pharmacokinetics, 20, 294–299.
   PubMedGoogle Scholar
• Eichelbaum, M., Baur, M.P., Dengler, H.J., Osikowska-Evers, B.O., Tieves, G., Zekorn, C. & Rittner, C. (1987). Chromosomal assignment of human cytochrome P-450 (debrisoquine/sparteine type) to chromosome 22. British Journal of Clnical Pharmacology, 23, 455–458.
   PubMed Web of Science ®Google Scholar
• Eichelbaum, M., Spannbrucker, N., Steincke, B. & Dengler, H.J. (1979). Defective N-oxidation of sparteine in man: A new pharmacogenetic defect. European Journal of Clinical Pharmacology, 16, 183–187.
   PubMed Web of Science ®Google Scholar
• Fernandez, C.A., Smith, C., Yang, W., Lorier, R., Crews, K.R., Kornegay, N., … Broeckel, U. (2012). Concordance of DMET plus genotyping results with those of orthogonal genotyping methods. Clinical Pharmacology & Therapeutics, 92, 360–365.
   PubMed Web of Science ®Google Scholar
• Fohner, A., Muzquiz, L.I., Austin, M.A., Gaedigk, A., Gordon, A., Thornton, T., … Woodahl, E.L. (2013). Pharmacogenetics in American Indian populations: Analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai Tribes. Pharmacogenetics and Genomics, 23, 403–414.
   PubMed Web of Science ®Google Scholar
• Formea, C.M., Nicholson, W.T., McCullough, K.B., Berg, K.D., Berg, M.L., Cunningham, J.L., … Stollings, J.L. (2013). Development and evaluation of a pharmacogenomics educational program for pharmacists. American Journal of Pharmaceutical Education, 77, 10.
   PubMed Web of Science ®Google Scholar
• Frank, D., Jaehde, U. & Fuhr, U. (2007). Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. European Journal of Clinical Pharmacology, 63, 321–333.
   PubMed Web of Science ®Google Scholar
• Funck-Brentano, C., Boëlle, P.Y., Verstuyft, C., Bornert, C., Becquemont, L. & Poirier, J.M. (2005). Measurement of CYP2D6 and CYP3A4 activity in vivo with dextromethorphan: sources of variability and predictors of adverse effects in 419 healthy subjects. European Journal of Clinical Pharmacology, 61, 821–829.
   PubMed Web of Science ®Google Scholar
• Furman, K.D., Grimm, D.R., Mueller, T., Holley-Shanks, R.R., Bertz, R.J., Williams, L.A., … Katz, D.A. (2004). Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics. Phamacogenetics, 14, 279–284.
   PubMedGoogle Scholar
• Gaedigk, A., Bradford, L.D., Alander, S.W. & Leeder, J.S. (2006). CYP2D6*36 gene arrangements within the CYP2D6 locus: association of CYP2D6*36 with poor metabolizer status. Drug Metabolism and Disposition, 34, 563–569.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Bradford, L.D., Marcucci, K.A. & Leeder, J.S. (2002). Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans. Clinical Pharmacology and Therapeutics, 72, 76–89.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A. & Coetsee, C. (2008). The CYP2D6 gene locus in South African Coloureds: Unique allele distributions, novel alleles and gene arrangements. European Journal of Clinical Pharmacology, 64, 465–475.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Eklund, J.D., Pearce, R.E., Leeder, J.S., Alander, S.W., Phillips, M.S., … Kennedy, M.J. (2007). Identification and characterization of CYP2D6*56B, an allele associated with the poor metabolizer phenotype. Clinical Pharmacology and Therapeutics, 81, 817–820.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Frank, D. & Fuhr, U. (2009). Identification of a novel non-functional CYP2D6 allele, CYP2D6*69, in a Caucasian poor metabolizer individual. European Journal of Clinical Pharmacology, 65, 97–100.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Fuhr, U., Johnson, C., Berard, L.A., Bradford, D. & Leeder, J.S. (2010). CYP2D7-2D6 hybrid tandems: identification of novel CYP2D6 duplication arrangements and implications for phenotype prediction. Pharmacogenomics, 11, 43–53.
   PubMedGoogle Scholar
• Gaedigk, A., Gotschall, R.R., Forbes, N.S., Simon, S.D., Kearns, G.L. & Leeder, J.S. (1999). Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics, 9, 669–682.
   PubMedGoogle Scholar
• Gaedigk, A., Isidoro-Garcia, M., Pearce, R.E., Sanchez, S., Garcia-Solaesa, V., Lorenzo-Romo, C., … Corey, S. (2010). Discovery of the nonfunctional CYP2D6*31 allele in Spanish, Puerto Rican, and US Hispanic populations. European Journal of Clinical Pharmacology, 66, 859–864.
   PubMedGoogle Scholar
• Gaedigk, A., Montane Jaime, L.K., Bertino, J.S., Jr., Berard, A., Pratt, V.M., Bradfordand, L.D. & Leeder, J.S. (2010). Identification of novel CYP2D7-2D6 hybrids: Non-functional and functional variants. Frontiers in Pharmacology, 1, 121.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Ndjountché, L., Divakaran, K., Dianne Bradford, L., Zineh, I., Oberlander, T.F., … Steven Leeder, J. (2007). Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Clinical Pharmacology and Therapeutics, 81, 242–251.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Ndjountché, L., Gaedigk, R., Leeder, J.S. & Bradford, L.D. (2003). Discovery of a novel nonfunctional cytochrome P450 2D6 allele, CYP2D*42, in African American subjects. Clinical Pharmacology & Therapeutics, 73, 575–576.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Ndjountché, L., Leeder, J.S. & Bradford, L. D. (2005). Limited association of the 2988G> A single nucleotide polymorphism with CYP2D6*41 in black subjects. Clinical Pharmacology and Therapeutics, 77, 228–230.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Ryder, D.L., Bradford, L.D. & Leeder, J.S. (2003). CYP2D6 poor metabolizer status can be ruled out by a single genotyping assay testing for the −1584G promoter polymorphism. Clinical Chemistry, 49, 1008–1011.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Simon, S.D., Pearce, R.E., Bradford, L.D., Kennedy, M.J. & Leeder, J.S. (2008). The CYP2D6 activity score: Translating genotype information into a qualitative measure of phenotype. Clinical Pharmacology and Therapeutics, 83, 234–242.
   PubMed Web of Science ®Google Scholar
• Gaedigk, A., Twist, G.P. & Leeder, J.S. (2012). CYP2D6, SULT1A1 and UGT2B17 copy number variation: Quantitative detection by multiplex PCR. Pharmacogenomics, 13, 91–111.
   PubMed Web of Science ®Google Scholar
• Gonzalez, F.J., Skoda, R.C., Kimura, S., Umeno, M., Zanger, U.M., Nebert, D.W., … Meyer, U.A. (1988). Characterization of the common defect in humans deficient in debrisoquin metabolism. Nature, 331, 442–446.
   PubMed Web of Science ®Google Scholar
• Gonzalez, F.J., Vilbois, F., Hardwick, J.P., McBride, O.W., Nebert, D.W., Gelboin, H.V. & Meyer, U.A. (1988). Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22. Genomics, 2, 174–179.
   PubMedGoogle Scholar
• Gough, A.C., Miles, J.S., Spurr, N.K., Moss, J.E., Gaedigk, A., Eichelbaum, M. & Wolf, C.R. (1990). Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature, 347, 773–776.
   PubMed Web of Science ®Google Scholar
• Hall-Flavin, D.K., Winner, J.G., Allen, J.D., Jordan, J.J., Nesheim, R.S., Snyder, K.A., … Mrazek, D.A. (2012). Using a pharmacogenomic algorithm to guide the treatment of depression. Translational Psychiatry, 2, e172.
   PubMed Web of Science ®Google Scholar
• Halling, J.N., Petersen, M.S., Damkier, P., Nielsen, F., Grandjean, P., Weihe, P.l., … Brøsen, K. (2005). Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. European Journal of Clinical Pharmacology, 61, 491–497.
   PubMed Web of Science ®Google Scholar
• Hanioka, N., Kimura, S., Meyer, U.A. & Gonzalez, F.J. (1990). The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934-A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3’ splice recognition site. American Journal of Human Genetics, 47, 994–1001.
   PubMed Web of Science ®Google Scholar
• He, Y.J. & McLeod, H.L. (2012). Ready when you are: Easing into preemptive pharmacogenetics. Clinical Pharmacology and Therapeutics, 92, 412–414.
   PubMedGoogle Scholar
• Hicks, J.K., Crews, K.R., Hoffman, J.M., Kornegay, N.M., Wilkinson, M.R., Lorier, R., … Relling, M.V. (2012). A clinician-driven automated system for integration of pharmacogenetic interpretations into an electronic medical record. Clinical Pharmacology and Therapeutics, 92, 563–566.
   PubMed Web of Science ®Google Scholar
• Hicks, J.K., Swen, J.J., Thorn, C.F., Sangkuhl, K., Kharasch, E.D., Ellingrod, V.L., … Stingl, J.C. (2013). Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clinical Pharmacology and Therapeutics, 93, 402–408.
   PubMed Web of Science ®Google Scholar
• Hosono, N., Kato, M., Kiyotani, K., Mushiroda, T., Takata, S., Sato, H., … Kubo, M. (2009). CYP2D6 genotyping for functional-gene dosage analysis by allele copy number detection. Clinical Chemistry, 55, 1546–1554.
   PubMed Web of Science ®Google Scholar
• Hu, O.Y., Tang, H.S., Lane, H.Y., Chang, W.H. & Hu, T.M. (1998). Novel single-point plasma or saliva dextromethorphan method for determining CYP2D6 activity. Journal of Pharmacology and Experimental Therapeutics, 285, 955–960.
   PubMedGoogle Scholar
• Ikenaga, Y., Fukuda, T., Fukuda, K., Nishida, Y., Naohara, M., Maune, H. & Azuma, J. (2005). The frequency of candidate alleles for CYP2D6 genotyping in the Japanese population with an additional respect to the −1584C to G substitution. Drug Metabolism and Pharmacokinetics, 20, 113–116.
   PubMedGoogle Scholar
• Ingelman-Sundberg, M. (2005). Genetic polymorphisms of cytochrome P4502D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics Journal, 5, 6–13.
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg, M. & Rodriguez-Antona, C. (2005). Pharmacogenetics of drug-metabolizing enzymes: Implications for a safer and more effective drug therapy. Philosophical Transactions of the Royal Society B, 360, 1563–1570.
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg, M. & Sim, S.C. (2010). Pharmacogenetic biomarkers as tools for improved drug therapy; emphasis on the cytochrome P450 system. Biochemical and Biophysical Research Communications, 396, 90–94.
   PubMedGoogle Scholar
• Ingelman-Sundberg, M., Sim, S.C., Gomez, A. & Rodriguez-Antona, C. (2007). Influence of cytochrome P450 polymorphisms on drug therapies: Pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacology & Therapeutics, 116, 496–526.
   PubMed Web of Science ®Google Scholar
• Jaja, C., Burke, W., Thummel, K., Edwards, K. & Veenstra, D.L. (2008). Cytochrome p450 enzyme polymorphism frequency in indigenous and native American populations: A systematic review. Community Genetics, 11, 141–149.
   PubMedGoogle Scholar
• Johansson, I., Lundqvist, E., Bertilsson, L., Dahl, M.-L., Sjöqvist, F. & Ingelman-Sundberg, M. (1993). Inherited amplification of an active gene in the cytochrome P450 CYP2D6 locus as a cause of ultrarapid metabolism of debrisoquine. Proceedings of the National Academy of Sciences, 90, 11825–11829.
   PubMed Web of Science ®Google Scholar
• Johansson, I., Lundqvist, E., Dahl, M.-L. & Ingelman-Sundberg, M. (1996). PCR-based genotyping for duplicated and deleted CYP2D6 genes. Pharmacogenetics, 6, 351–355.
   PubMedGoogle Scholar
• Johansson, I., Oscarson, M., Yue, Q.-Y., Bertilsson, L., Sjöqvist, F. & Ingelman-Sundberg, M. (1994). Genetic analysis of the Chinese cytochrome P4502D locus: Characterization of variant CYP2D6 genes in subjects with diminished capacity for debrisoquine hydroxylation. Molecular Pharmacology, 46, 452–459.
   PubMed Web of Science ®Google Scholar
• Johnson, J.A., Burkley, B.M., Langaee, T.Y., Clare-Salzler, M.J., Klein, T.E. & Altman, R.B. (2012). Implementing personalized medicine: Development of a cost-effective customized pharmacogenetics genotyping array. Clinical Pharmacology & Therapeutics, 92, 437–439.
   PubMed Web of Science ®Google Scholar
• Jurica, J., Bartecek, R., Zourkova, A., Pindurova, E., Sulcova, A., Kasparek, T. & Zendulka, O. (2012). Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice. Jourmal of Clinical Pharmacology and Therapeutics, 37, 486–490.
   PubMed Web of Science ®Google Scholar
• Kagimoto, M., Heim, M., Kagimoto, K., Zeugin, T. & Meyer, U.A. (1990). Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. Jourmal of Biological Chemistry, 265, 17209–17214.
   PubMed Web of Science ®Google Scholar
• Kelly, C.M. & Pritchard, K.I. (2012). CYP2D6 genotype as a marker for benefit of adjuvant tamoxifen in postmenopausal women: lessons learned. Journal of the National Cancer Institute, 104, 427–428.
   PubMedGoogle Scholar
• Kim, E.Y., Lee, S.S., Jung, H.J., Jung, H.E., Yeo, C.W., Shon, J.H. & Shin, J.G. (2010). Robust CYP2D6 genotype assay including copy number variation using multiplex single-base extension for Asian populations. Clinica Chimica Acta, 411, 2043–2048.
   PubMed Web of Science ®Google Scholar
• Kim, J., Lee, S.Y. & Lee, K.A. (2012). Copy number variation and gene rearrangements in CYP2D6 genotyping using multiplex ligation-dependent probe amplification in Koreans. Pharmacogenomics, 13, 963–973.
   PubMedGoogle Scholar
• Kimura, S., Umeno, M., Skoda, R.C., Meyer, U.A. & Gonzalez, F.J. (1989). The human debrisoquine 4-hydroxylase (CYP2D) locus: Sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. American Journal of Human Genetics, 45, 889–904.
   PubMed Web of Science ®Google Scholar
• Kirchheiner, J., Heesch, C., Bauer, S., Meisel, C., Seringer, A., Goldammer, M., … Brockmöller, J. (2004). Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetics and pharmacodynamics. Clinical Pharmacology and Therapeutics, 76, 302–312.
   PubMed Web of Science ®Google Scholar
• Kirchheiner, J., Henckel, H.B., Franke, L., Meineke, I., Tzvetkov, M., Uebelhack, R., … Brockmöller, J. (2005). Impact of the CYP2D6 ultrarapid metabolizer genotype on doxepin pharmacokinetics and serotonin in platelets. Pharmacogenetics and Genomics, 15, 579–587.
   PubMed Web of Science ®Google Scholar
• Kirchheiner, J., Henckel, H.B., Meineke, I., Roots, I. & Brockmöller, J. (2004). Impact of the CYP2D6 ultrarapid metabolizer genotype on mirtazapine pharmacokinetics and adverse events in healthy volunteers. Journal of Clinical Psychopharmacology, 24, 647–652.
   PubMed Web of Science ®Google Scholar
• Kirchheiner, J., Schmidt, H., Tzvetkov, M., Keulen, J.-T., Lötsch, J., Roots, I. & Brockmöller, J. (2007). Pharmacokinetics of codeine and its metabolite morphine in ultrarapid metabolizers due to CYP2D6 duplication. Pharmacogenomics Journal, 4, 257–265.
   Google Scholar
• Kitada, M. (2003). Genetic polymorphism of cytochrome P450 enzymes in Asian populations: Focus on CYP2D6. International Journal of Clinical Pharmacology Research, 23, 31–35.
   PubMedGoogle Scholar
• Kohlrausch, F.B., Gama, C.S., Lobato, M.I., Belmonte-de-Abreu, P., Gesteira, A., Barros, F., … Hutz, M.H. (2009). Molecular diversity at the CYP2D6 locus in healthy and schizophrenic southern Brazilians. Pharmacogenomics, 10, 1457–1466.
   PubMed Web of Science ®Google Scholar
• Kramer, W.E., Walker, D.L., O’Kane, D.J., Mrazek, D.A., Fisher, P.K., Dukek, B.A., … Black, J.L. (2009). CYP2D6: Novel genomic structures and alleles. Pharmacogenetics and Genomics, 19, 813–822.
   PubMed Web of Science ®Google Scholar
• Kumar, S., Bellis, C., Zlojutro, M., Melton, P.E., Blangero, J. & Curran, J.E. (2011). Large scale mitochondrial sequencing in Mexican Americans suggests a reappraisal of Native American origins. BMC Evolutionary Biology, 11, 293.
   PubMed Web of Science ®Google Scholar
• Leandro-Garcia, L.J., Leskela, S., Montero-Conde, C., Landa, I., Lopez-Jimenez, E., Leton, R., … Rodriguez-Antona, C. (2009). Determination of CYP2D6 gene copy number by multiplex polymerase chain reaction analysis. Analytical Biochemistry, 389, 74–76.
   PubMedGoogle Scholar
• Lee, S.J., Lee, S.S., Jung, H.J., Kim, H.S., Park, S.J., Yeo, C.W. & Shin, J.G. (2009). Discovery of novel functional variants and extensive evaluation of CYP2D6 genetic polymorphisms in Koreans. Drug Metabolism and Disposition, 37, 1464–1470.
   PubMed Web of Science ®Google Scholar
• Leeder, J.S., Pearce, R.E., Gaedigk, A., Modak, A. & Rosen, D.I. (2008). Evaluation of a [13C]-dextromethorphan breath test to assess CYP2D6 phenotype. Journal of Clinical Pharmacology, 48, 1041–1051.
   PubMed Web of Science ®Google Scholar
• Li, L., Pan, R.-M., Porter, T.D., Jensen, N.S., Silber, P., Russo, G., … Wedlund, P.J. (2006). New cytochrome P450 2D6*56 allele identified by genotype/phenotype analysis of cryopreserved human hepatocytes. Drug Metabolism and Disposition, 34, 1411–1416.
   PubMed Web of Science ®Google Scholar
• Liao, H.W., Tsai, I.L., Chen, G.Y., Kuo, C.T., Wei, M.F., Hwang, T.J., … Kuo, C.H. (2013). Simultaneous detection of single nucleotide polymorphisms and copy number variations in the CYP2D6 gene by multiplex polymerase chain reaction combined with capillary electrophoresis. Analytica Chimica Acta, 763, 67–75.
   PubMed Web of Science ®Google Scholar
• Llerena, A., Dorado, P. & Penas-Lledo, E.M. (2009). Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics, 10, 17–28.
   PubMed Web of Science ®Google Scholar
• Llerena, A., Dorado, P., Ramirez, R., Gonzalez, I., Alvarez, M., Penas-Lledo, E.M., … Calzadilla, L.R. (2010). CYP2D6 genotype and debrisoquine hydroxylation phenotype in Cubans and Nicaraguans. Pharmacogenomics Journal.
   Google Scholar
• Løvlie, R., Daly, A.K., Idle, J.R. & Steen, V.M. (1997). Characterization of the 16 + 9 kb and 30 + 9 kb CYP2D6. Pharmacogenetics, 7, 149–152.
   PubMedGoogle Scholar
• Løvlie, R., Daly, A.K., Molven, A., Idle, J.R. & Steen, V.M. (1996). Ultrarapid metabolizers of debrisoquine: Characterization and PCR-based detection of alleles with duplication of the CYP2D6 gene. FEBS Letters, 392, 30–34.
   PubMed Web of Science ®Google Scholar
• Lundqvist, E., Johansson, I. & Ingelman-Sundberg, M. (1999). Genetic mechanism for duplication and multiduplication of the CYP2D6 gene. Gene, 226, 327–338.
   PubMed Web of Science ®Google Scholar
• Mahgoub, A., Idle, J.R., Dring, L.G., Lancaster, R. & Smith, R.L. (1977). Polymorphic hydroxylation of Debrisoquine in man. Lancet, 2, 584–586.
   PubMed Web of Science ®Google Scholar
• Marez, D., Legrand, M., Sabbagh, N., Guidice, J.-M., Spire, C., Lafitte, J.-J., … Broly, F. (1997). Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: Characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics, 7, 193–202.
   PubMedGoogle Scholar
• Matimba, A., Del-Favero, J., Van Broeckhoven, C. & Masimirembwa, C. (2009). Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects. Human Genomics, 3, 169–190.
   PubMedGoogle Scholar
• Meyer, U.A. (2004). Pharmacogenetics – Five decades of therapeutic lessons from genetic diversity. Nature Reviews Genetics, 5, 669–676.
   PubMed Web of Science ®Google Scholar
• Moen, M. & Lamba, J. (2012). Assessment of healthcare students’ views on pharmacogenomics at the University of Minnesota. Pharmacogenomics, 13, 1537–1545.
   PubMedGoogle Scholar
• Montane Jaime, L.K., Lalla, A., Steimer, W. & Gaedigk, A. (2013). Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: Discovery of novel allelic variants. Pharmacogenomics, 14, 261–276.
   PubMed Web of Science ®Google Scholar
• Mrazek, D.A. (2010). Psychiatric pharmacogenomic testing in clinical practice. Dialogues in Clinical Neuroscience, 12, 69–76.
   PubMedGoogle Scholar
• Mrazek, D.A. & Lerman, C. (2011). Facilitating clinical implementation of pharmacogenomics. Journal of the American Medical Association, 306, 304–305.
   Google Scholar
• Myrand, S.P., Sekiguchi, K., Man, M.Z., Lin, X., Tzeng, R.Y., Teng, C.H., … Wilner, K.D. (2008). Pharmacokinetics/ genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations. Clinical Pharmacology & Therapeutics, 84, 347–361.
   PubMed Web of Science ®Google Scholar
• Nakamura, N., Fukuda, T., Nonen, S., Hashimoto, K., Azuma, J. & Gemma, N. (2010). Simple and accurate determination of CYP2D6 gene copy number by a loop-mediated isothermal amplification method and an electrochemical DNA chip. Clinica Chimica Acta, 411, 568–573.
   PubMedGoogle Scholar
• Nakamura, Y., Ratain, M.J., Cox, N.J., McLeod, H.L., Kroetz, D.L. & Flockhart, D.A. (2012). Re: 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, 1264; author reply 1266–1268.
   PubMedGoogle Scholar
• O’Donnell, P.H., Bush, A., Spitz, J., Danahey, K., Saner, D., Das, S., … Ratain, M.J. (2012). The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics. Clinical Pharmacology and Therapeutics, 92, 446–449.
   PubMed Web of Science ®Google Scholar
• Oscarson, M., Hidestrand, M., Johansson, I. & Ingelman-Sundberg, M. (1997). A combination of mutations in the CYP2D6*17 (CYP2D6Z) allele causes alterations in enzyme function. Molecular Pharmacology, 32, 1034–1040.
   Google Scholar
• Panserat, S., Mura, C., Gerard, N., Vincent-Viry, M., Galteau, M.M., Jacq-Aigrain, E. & Krishnamoorthy, R. (1995). An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype. British Journal of Clinical Pharmacology., 40, 361–367.
   PubMed Web of Science ®Google Scholar
• Perego, U.A., Angerhofer, N., Pala, M., Olivieri, A., Lancioni, H., Hooshiar Kashani, B., … Torroni, A. (2010). The initial peopling of the Americas: A growing number of founding mitochondrial genomes from Beringia. Genome Research, 20, 1174–1179.
   PubMed Web of Science ®Google Scholar
• Pharoah, P.D., Abraham, J. & Caldas, C. (2012). Re: CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: The Breast International Group 1-98 trial and re: CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. Journal of the National Cancer Institute, 104, 1263–1264; author reply 1266–1268.
   PubMedGoogle Scholar
• Preissner, S., Kroll, K., Dunkel, M., Senger, C., Goldsobel, G., Kuzman, D., … Preissner, R. (2010). SuperCYP: A comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Research, 38, D237–243.
   PubMed Web of Science ®Google Scholar
• Qin, S., Shen, L., Zhang, A., Xie, J., Shen, W., Chen, L., … Xing, Q. (2008). Systematic polymorphism analysis of the CYP2D6 gene in four different geographical Han populations in mainland China. Genomics, 92, 152–158.
   PubMed Web of Science ®Google Scholar
• Qumsieh, R.Y., Ali, B.R., Abdulrazzaq, Y.M., Osman, O., Akawi, N.A. & Bastaki, S.M. (2011). Identification of new alleles and the determination of alleles and genotypes frequencies at the CYP2D6 gene in Emiratis. Public Library of Sciene One, 6, e28943.
   Google Scholar
• Rae, J.M., Drury, S., Hayes, D.F., Stearns, V., Thibert, J.N., Haynes, B.P., … Dowsett, M. (2012). CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. Journal of the National Cancer Institute, 104, 452–460.
   PubMed Web of Science ®Google Scholar
• Raimundo, S., Fischer, J., Eichelbaum, M., Griese, E.-U., Schwab, M. & Zanger, U.M. (2000). Elucidation of the genetic basis of the common ‘intermediate metabolizer’ phenotype for drug oxidation by CYP2D6. Pharmacogenetics, 10, 577–581.
   PubMedGoogle Scholar
• Raimundo, S., Toscano, C., Klein, K., Fischer, J., Griese, E.-U., Eichelbaum, M., … Zanger, U.M. (2004). A novel intronic mutation, 2988G> A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects. Clinical Pharmacology and Therapeutics, 76, 128–138.
   PubMed Web of Science ®Google Scholar
• Ramamoorthy, A. & Skaar, T.C. (2011). Gene copy number variations: It is important to determine which allele is affected. Pharmacogenomics, 12, 299–301.
   PubMedGoogle Scholar
• Rasmussen, H.B. & Werge, T. (2011). Novel variant of CYP2D6*6 is undetected by a commonly used genotyping procedure. Pharmacological Reports, 63, 1264–1266.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Relling, M.V. & Klein, T.E. (2011). CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clinical Pharmacology and Therapeutics, 89, 464–467.
   PubMed Web of Science ®Google Scholar
• Rosenberg, N.A., Mahajan, S., Ramachandran, S., Zhao, C., Pritchard, J.K. & Feldman, M.W. (2005). Clines, clusters, and the effect of study design on the inference of human population structure. Public Library of Science Genetics, 1, e70.
   Google Scholar
• Sachse, C., Brockmöller, J., Bauer, S. & Roots, I. (1997). Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences. American Journal of Human Genetics, 60, 284–295.
   PubMed Web of Science ®Google Scholar
• Sachse, C., Brockmöller, J., Hildebrand, M., Müller, K. & Roots, I. (1998). Correctness of prediction of the CYP2D6 phenotype confirmed by genotyping 47 intermediate and poor metabolizers of debrisoquine. Pharmacogenetics, 8, 181–185.
   PubMedGoogle Scholar
• Sakuyama, K., Sasaki, T., Ujiie, S., Obata, K., Mizugaki, M., Ishikawa, M. & Hiratsuka, M. (2008). Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A–B, 18, 27, 36, 39, 47–51, 53–55, and 57). Drug Metabolism and Disposition. doi:10.1124/dmd.108.023242.
   PubMedGoogle Scholar
• Schaeffler, E., Schwab, M., Eichelbaum, M. & Zanger, U.M. (2003). CYP2D6 genotyping strategy based on gene copy number determination by TaqMan real-time PCR. Human Mutation, 22, 476–485.
   PubMedGoogle Scholar
• Schmid, B., Bircher, J., Preisig, R. & Küpfer, A. (1985). Polymorphic dextromethorphan metabolism: Co-segregation of oxidative O-demethylation with debrisoquine hydroxylation. Clinical Pharmacology and Therapeutics, 38, 618–624.
   PubMed Web of Science ®Google Scholar
• Scott, S.A. (2011). Personalizing medicine with clinical pharmacogenetics. Genetics in Medicine, 13, 987–995.
   PubMed Web of Science ®Google Scholar
• Selkirk, C.G., Weissman, S.M., Anderson, A. & Hulick, P.J. (2013). Physicians’ preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genetic Testing and Molecular Biomarkers, 17, 219–225.
   PubMed Web of Science ®Google Scholar
• Seripa, D., Pilotto, A., Panza, F. & Matera, M.G. (2010). Pharmacogenetics of cytochrome P450 (CYP) in the elderly. Ageing Research Reviews, 9, 457–474.
   PubMed Web of Science ®Google Scholar
• Sim, S.C., Altman, R.B. & Ingelman-Sundberg, M. (2011). Databases in the area of pharmacogenetics. Human Mutation, 32, 526–531.
   PubMed Web of Science ®Google Scholar
• Sim, S.C., Daly, A.K. & Gaedigk, A. (2012). CYP2D6 update: Revised nomenclature for CYP2D7/2D6 hybrid genes. Pharmacogenetics and Genomics, 22, 692–694.
   PubMedGoogle Scholar
• Sim, S.C. & Ingelman-Sundberg, M. (2010). The Human Cytochrome P450 (CYP) Allele Nomenclature website: A peer-reviewed database of CYP variants and their associated effects. Human Genomics, 4, 278–281.
   PubMedGoogle Scholar
• Sim, S.C. & Ingelman-Sundberg, M. (2013). Update on allele nomenclature for human cytochromes P450 and the Human Cytochrome P450 Allele (CYP-Allele) Nomenclature Database. Methods in Molecular Biology, 987, 251–259.
   PubMedGoogle Scholar
• Sistonen, J., Sajantila, A., Lao, O., Corander, J., Barbujani, G. & Fuselli, S. (2007). CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenetics and Genomics, 17, 93–101.
   PubMed Web of Science ®Google Scholar
• Skoda, R.C., Gonzalez, F.J., Demierre, A. & Meyer, U.A. (1988). Two mutant alleles of the human cytochrome P-450db1 gene (P450C2D1) associated with genetically deficient metabolism of debrisoquine and other drugs. Proceedings of the National Academy of Sciences USA, 85, 5240–5243.
   PubMed Web of Science ®Google Scholar
• Söderbäck, E., Zackrisson, A.-L., Lindblom, B. & Alderborn, A. (2005). Determination of CYP2D6 gene copy number by pyrosequencing. Clinical Chemistry, 51, 522–531.
   PubMedGoogle Scholar
• Soyama, A., Kubo, T., Miyajima, A., Saito, Y., Shiseki, K., Komamura, K., … Sawada, J. (2004). Novel nonsynonymous single nucleotide polymorphisms in the CYP2D6 gene. Drug Metabolism and Pharmacokinetics, 19, 313–319.
   PubMedGoogle Scholar
• Squassina, A., Manchia, M., Manolopoulos, V.G., Artac, M., Lappa-Manakou, C., Karkabouna, S., … Patrinos, G.P. (2010). Realities and expectations of pharmacogenomics and personalized medicine: Impact of translating genetic knowledge into clinical practice. Pharmacogenomics, 11, 1149–1167.
   PubMed Web of Science ®Google Scholar
• Stanton, V., Jr. (2012). Re: 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, 1265–1266; author reply 1266–1268.
   PubMedGoogle Scholar
• Suarez-Kurtz, G., Pena, S.D., Struchiner, C.J. & Hutz, M.H. (2012). Pharmacogenomic diversity among Brazilians: Influence of ancestry, self-reported color, and geographical origin. Frontiers in Pharmacology, 3, 191.
   PubMed Web of Science ®Google Scholar
• Swen, J.J., Huizinga, T.W., Gelderblom, H., de Vries, E.G., Assendelft, W.J., Kirchheiner, J. & Guchelaar, H.J. (2007). Translating pharmacogenomics: Challenges on the road to the clinic. Public Library of Science Medicine, 4, e209.
   Google Scholar
• Swen, J.J., Nijenhuis, M., de Boer, A., Grandia, L., Maitland- van der Zee, A.H., Mulder, H., … Guchelaar, H.J. (2011). Pharmacogenetics: From bench to byte – An update of guidelines. Clinical Pharmacology and Therapeutics, 89, 662–673.
   PubMed Web of Science ®Google Scholar
• Tateishi, T., Chida, M., Ariyoshi, N., Mizorogi, Y., Kamataki, T. & Kobayashi, S. (1999). Analysis of the CYP2D6 gene in relation to dextromethorphan O-demethylation capacity in a Japanese population. Clinical Pharmacology and Therapeutics, 65, 570–575.
   PubMed Web of Science ®Google Scholar
• Teh, L.K. & Bertilsson, L. (2012). Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance. Drug Metabolism and Pharmacokinetics, 27, 55–67.
   PubMed Web of Science ®Google Scholar
• Thorn, C.F., Klein, T.E. & Altman, R.B. (2010). Pharmacogenomics and bioinformatics: PharmGKB. Pharmacogenomics, 11, 501–505.
   PubMed Web of Science ®Google Scholar
• Toscano, C., Klein, K., Blievernicht, J., Schaeffeler, E., Saussele, T., Raimundo, S., … Zanger, U.M. (2006). Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41 allele caused by the intronic SNP 2988G> A: Evidence for modulation of splicing events. Pharmacogenetics and Genomics, 16, 755–766.
   PubMed Web of Science ®Google Scholar
• Tutton, R. (2012). Personalizing medicine: futures present and past. Social Science and Medicine, 75, 1721–1728.
   PubMed Web of Science ®Google Scholar
• von Ahsen, N., Tzvetkov, M., Karunajeewa, H.A., Gomorrai, S., Ura, A., Brockmöller, J., … Oellerich, M. (2010). CYP2D6 and CYP2C19 in Papua New Guinea: High frequency of previously uncharacterized CYP2D6 alleles and heterozygote excess. International Journal of Molecular Epidemiology and Genetics, 1, 310–319.
   PubMedGoogle Scholar
• Warnich, L., Drögemöller, B.I., Pepper, M.S., Dandara, C. & Wright, G.E. (2011). Pharmacogenomic research in South Africa: Lessons learned and future opportunities in the rainbow nation. Current Pharmacogenomics and Personalized Medicine, 9, 191–207.
   PubMedGoogle Scholar
• Wennerholm, A., Dandara, C., Sayi, J., Svensson, J.-O., Abdi, Y.A., Ingelman-Sundberg, M., … Gustafsson, L.L. (2002). The African-specific CYP2D6*17 allele encodes an enzyme with changed substrate specificity. Clinical Pharmacology and Therapeutics, 71, 77–88.
   PubMed Web of Science ®Google Scholar
• Wennerholm, A., Johansson, I., Hidestrand, M., Bertilsson, L., Gustafsson, L.L. & Ingelman-Sundberg, M. (2001). Characterization of theCYP2D6*29 allele commonly present in a black Tanzanian population causing reduced catalytic activity. Pharmacogenetics, 11, 417–427.
   PubMedGoogle Scholar
• Whirl-Carrillo, M., McDonagh, E.M., Hebert, J.M., Gong, L., Sangkuhl, K., Thorn, C.F., … Klein, T.E. (2012). Pharmacogenomics knowledge for personalized medicine. Clinical Pharmacology and Therapeutics, 92, 414–417.
   PubMed Web of Science ®Google Scholar
• Winner, J.G., Goebert, D., Matsu, C. & Mrazek, D.A. (2010). Training in psychiatric genomics during residency: A new challenge. Academic Psychiatry, 34, 115–118.
   PubMed Web of Science ®Google Scholar
• Wong, W.B., Carlson, J.J., Thariani, R. & Veenstra, D.L. (2010). Cost effectiveness of pharmacogenomics: A critical and systematic review. Pharmacoeconomics, 28, 1001–1013.
   PubMed Web of Science ®Google Scholar
• Wright, G.E., Niehaus, D.J., Drögemöller, B.I., Koen, L., Gaedigk, A. & Warnich, L. (2010). Elucidation of CYP2D6 genetic diversity in a unique African population: Implications for the future application of pharmacogenetics in the Xhosa population. Annals of Human Genetics, 74, 340–350.
   PubMed Web of Science ®Google Scholar
• Yamazaki, H., Kiyotani, K., Tsubuko, S., Matsunaga, M., Fujieda, M., Saito, T., … Kamataki, T. (2003). Two novel haplotypes of CYP2D6 gene in a Japanese population. Drug Metabolism and Pharmacokinetics, 18, 269–271.
   PubMedGoogle Scholar
• Yang, X., Zhang, B., Molony, C., Chudin, E., Hao, K., Zhu, J., … Lum, P.Y. (2010). Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. Genome Research, 20, 1020–1036.
   PubMed Web of Science ®Google Scholar
• Yokoi, T., Kosaka, Y., Chida, M., Chiba, K., Nakamura, H., Ishizaki, T., … Kamataki, T. (1996). A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype. Pharmacogenetics, 6, 395–401.
   PubMedGoogle Scholar
• Zanger, U.M., Raimundo, S. & Eichelbaum, M. (2004). Cytochrome P450 2D6: Overview and update on pharmacology, genetics, biochemistry. Naunyn-Schmiedeberg’s Archives of Pharmacology, 369, 23–37.
   PubMed Web of Science ®Google Scholar
• Zanger, U.M. & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology and Therapeutics, 138, 103–141.
   PubMed Web of Science ®Google Scholar
• Zanger, U.M., Turpeinen, M., Klein, K. & Schwab, M. (2008). Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and Bioanalytical Chemistry, 392, 1093–1108.
   PubMed Web of Science ®Google Scholar
• Zhang, W.Y., Tu, Y.B., Haining, R.L. & Yu, A.M. (2009). Expression and functional analysis of CYP2D6.24, CYP2D6.26, CYP2D6.27, and CYP2D7 isozymes. Drug Metabolism and Disposition, 37, 1–4.
   PubMed Web of Science ®Google Scholar
• Zhou, S.F. (2009a). Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clinical Pharmacokinetics, 48, 689–723.
   PubMed Web of Science ®Google Scholar
• Zhou, S.F. (2009b). Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clinical Pharmacokinetics, 48, 761–804.
   PubMed Web of Science ®Google Scholar