Genetic Polymorphism in Cytochrome P450 2D6 (CYP2D6): Population Distribution of CYP2D6 Activity

REFERENCES

• Agundez , J. , Ledesma , M. and Ladero , J. 1995 . Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population . Clin. Pharmacol. Ther. , 57 : 265 – 269 .
   PubMed Web of Science ®Google Scholar
• Aklillu , E. , Persson , I. , Bertilsson , L. , Johansson , I. , Rodriguez , F. and Ingelman-Sundberg , I. 1996 . Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles . J. Pharmacol. Exp. Ther. , 278 : 441 – 446 .
   PubMed Web of Science ®Google Scholar
• Alcorn , J. and McNamara , PJ. 2002 . Ontogeny of hepatic and renal systemic clearance pathways in infants . Clin. Pharmacokinet. , 41 : 959 – 998 .
   PubMed Web of Science ®Google Scholar
• Allorge , D. , Breant , D. , Harlow , J. , Chowdry , J. , Lo-Guidice , JM. , Chevalier , D. , Cauffiez , C. , Lhermitte , M. , Blaney , F. E. , Tucker , G. T. , Broly , F. and Ellis , S. W. 2005 . Functional analysis of CYP2D6.31 variant: homology modeling suggests possible disruption of redox partner interaction by Arg440his substitution . Proteins , 59 : 339 – 346 .
   PubMed Web of Science ®Google Scholar
• Antonarakis , S. E. 1998 . Recommendations for a nomenclature system for human gene mutations. Nomenclature working group . Hum. Mutat. , 11 : 1 – 3 .
   PubMed Web of Science ®Google Scholar
• Anwar , W. , Abdel-Rahman , S. , El Zein , R. , Mostafa , H. and Au , W. 1996 . Genetic polymorphism of GSTM1, CYP2E1 and CYP2D6 in Egyptian bladder cancer patients . Carcinogenesis , 17 : 1923 – 1929 .
   PubMed Web of Science ®Google Scholar
• Ayesh , R. , Idle , J. , Ritchie , J. C. , Crothers , M. J. and Hetzel , M. 1984 . Metabolic oxidation phenotypes as markers for susceptibility to lung cancer . Nature , 312 : 169 – 170 .
   PubMed Web of Science ®Google Scholar
• Aynacioglu , AS. , Sachse , C. , Bozkurt , A. , Kortunay , S. , Nacak , M. , Schroder , T. , Kayaalp , SO. , Roots , I. and Brockmoller , J. 1999 . Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population . Clin. Pharmacol.Ther. , 66 : 185 – 192 .
   PubMed Web of Science ®Google Scholar
• Bear , W. L. and Teel , R. W. 2000 . Effects of citrus phytochemicals on liver and lung cytochrome P450 activity and on the in vitro metabolism of the tobacco-specific nitrosamine NNK . Anticancer Res. , 20 : 3323 – 2229 .
   PubMed Web of Science ®Google Scholar
• Benhamou , S. , Bouchardy , C. and Dayer , P. 1996 . Effects of CYP2D6 activity and tobacco on larynx cancer risk . Cancer Epidemiol. Biomarkers Prev. , 5 : 683 – 686 .
   PubMed Web of Science ®Google Scholar
• Bernal , ML , Sinues , B. , Johansson , I. , McLellan , RA. , Wennerholm , A. , Dahl , M. , Ingelman-Sundberg , M. and Bertilsson , L. 1999 . Ten percent of North Spanish individuals carry duplicated or triplicated CYP2D6 genes associated with ultrarapid metabolism of debrisoquine . Pharmacogenetics , 9 : 657 – 660 .
   PubMedGoogle Scholar
• Bertilsson , L. , Lou , Y. , Du , Y. , Liu , Y. , Kuang , T. , Liao , X. , Wany , K. , Reviriego , J. , Iselius , L. and Sjoqvist , F. 1992 . Pronounced differences between native Chinese and Swedish populations in the polymorphis hydroxylations of debrisoquin and s-mephenytoin . Clin. Pharmacol.Ther. , 51 : 388 – 397 .
   PubMed Web of Science ®Google Scholar
• Bertz , R. J. and Granneman , G. R. 1997 . Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions . Clin. Pharmacokinet. , 32 : 210 – 258 .
   PubMed Web of Science ®Google Scholar
• Bogni , A. , Monshouwer , M. , Moscone , A. , Hidestrand , M. , Ingelman-Sundberg , M. , Hartung , T. and Coecke , S. 2005 . Substrate specific metabolism by polymorphic cytochrome P450 2D6 alleles . Toxicol. In Vitro , 19 : 621 – 629 .
   PubMed Web of Science ®Google Scholar
• Bosch , T. M. , Doodeman , V. D. , Smits , P. H. , Meijerman , I. , Schellens , J. H. and Beijnen , J. H. 2006 . Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a Dutch population . Mol. Diagn. Ther. , 10 : 175 – 185 .
   PubMed Web of Science ®Google Scholar
• Bouchardy , C. , Benhamou , S. and Dayer , P. 1996 . The effect of tobacco on lung cancer risk depends on CYP2D6 activity . Cancer Res. , 56 : 251 – 253 .
   PubMed Web of Science ®Google Scholar
• Bouchardy , C. , Benhamou , S. , Jourenkova , N. , Dayer , P. and Hirvoven , A. 2001 . Metabolic genetic polymorphisms and susceptibility to lung cancer . Lung Cancer , 32 : 109 – 112 .
   PubMed Web of Science ®Google Scholar
• Boyer , E. W. , Quang , L. , Woolf , A. and Shannon , M. 2001 . Dextromethorphan and ecstasy pills . J. Am. Med. Assoc. , 285 : 409 – 410 .
   Google Scholar
• Branch , R. , Chern , H. , Adedoyin , A. , Romkes-Sparks , M. , Lesnick , T. , Persad , R. , Wilkinson , G. , Fleming , C. , Dickinson , A. and Sibley , G. 1995 . The procarcinogen hypothesis for bladder cancer: Activities of individual drug metabolizing enzymes as risk factors . Pharmacogenetics , 5 : S97 – S102 .
   PubMedGoogle Scholar
• Brockmoller , J. , Cascorbi , I. , Kerb , R. and Roots , I. 1996 . Combined analysis of inherited polymorphisms in arlyamine N-acetyltransferase 2, glutathione S-transferases M1 and TI, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk . Cancer Res. , 56 : 3915 – 3925 .
   PubMed Web of Science ®Google Scholar
• Butler , A. M. and Murray , M. 1997 . Biotransformation of parathion in human liver: Participation of CYP3A4 and its inactivation during microsomal parathion activation . J. Pharmacol. Exp. Ther. , 280 : 966 – 973 .
   PubMed Web of Science ®Google Scholar
• Caccia , S. 2000 . Biotransformation of post-clozapine antipsychotics . Clin. Pharmacokinet. , 38 : 393 – 414 .
   PubMed Web of Science ®Google Scholar
• Cai , W. M. , Nikoloff , D. M. , Pan , R. M. , de Leon , J. , Fanti , P. , Fairchild , M. , Koch , W. H. and Wedlund , P. J. 2006 . CYP2D6 genetic variation in healthy adults and psychiatric African-American subjects: Implications for clinical practice and genetic testing . Pharmacogenom. J. , 6 : 343 – 350 .
   PubMed Web of Science ®Google Scholar
• Caporaso , N. , Hayes , RB. , Dosemeci , M. , Hoover , R. , Ayesh , R. , Hetzel , M. and Idle , J. 1989 . Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype . Cancer Res. , 49 : 3675 – 3679 .
   PubMed Web of Science ®Google Scholar
• Caporaso , N. E. , Tucker , M. A. and Hoover , R. N. 1990 . Lung cancer and the debrisoquine metabolic phenotype . JNCI , 82 : 1264 – 1272 .
   PubMed Web of Science ®Google Scholar
• Cascorbi , I. 2003 . Pharmacogenetics of cytochrome p4502D6: Genetic background and clinical implication . Eur. J. Clin. Invest. , 33 : 17 – 22 .
   PubMed Web of Science ®Google Scholar
• Cho , H. Y. and Lee , Y. B. 2006 . Pharmacokinetics and bioequivalence evaluation of risperidone in healthy male subjects with different CYP2D6 genotypes . Arch. Pharm. Res. , 29 : 525 – 533 .
   PubMedGoogle Scholar
• Christensen , P. M. , Gotzsche , P. C. and Brosen , K. 1997 . The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of lung cancer: A meta-analysis . Eur. J. Clin. Pharmacol. , 51 : 389 – 393 .
   PubMedGoogle Scholar
• Christensen , P. M. , Gotzsche , P. C. and Brosen , K. 1998 . The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease: A meta-analysis . Pharmacogenetics , 8 : 473 – 479 .
   PubMedGoogle Scholar
• Coleman , T. , Ellis , S. , Martin , I. , Lennard , M. and Tucker , G. 1996 . 1-Methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) is N-demethylated by cytochromes P450 2D6, 1A2 and 3A4—Implications for susceptibility to Parkinson's disease . J. Pharmacol. Exp. Ther. , 277 : 685 – 690 .
   PubMed Web of Science ®Google Scholar
• Crespi , C. L. , Penman , B. W. , Gelboin , H. V. and Gonzalez , F. S. 1991 . A tobacco smoke-derived nitrosamine, 4-(methlynitrosamino)-1-(3-pyridyl)-1-butanone, is activated by multiple human cytochrome P450s including the polymorphic human cytochrome P450 2D6 . Carcinogenesis , 12 : 1197 – 1201 .
   PubMed Web of Science ®Google Scholar
• Dahl , M. , Johansson , I. , Bertilsson , L. , Ingelman-Sunberg , M. and Sjoqvist , F. 1995a . Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis . J. Pharmacol. Exp. Ther. , 274 : 515 – 520 .
   Google Scholar
• Dahl , M. , Yue , Q. , Roh , H. , Johansson , I. , Sawe , J. , Sjoqvist , F. and Bertilsson , L. 1995b . Genetic analysis of the CYP2D locus in relation to debrisoquine hydroxylation capacity in Korean, Japanese, and Chinese subjects . Pharmacogenetics , 5 : 159 – 164 .
   PubMedGoogle Scholar
• Dalen , P. , Dahl , M. , Ruiz , M. , ResEng , J. N. and Bertilsson , L. 1998 . 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes . Clin. Pharmacol.Ther. , 63 : 444 – 452 .
   PubMed Web of Science ®Google Scholar
• Dalen , P. , Dahl , M. , Eichelbaum , M. , Bertilsson , L. and Wilkinson , G. R. 1999 . Disposition of debrisoquine in Caucasians with different CYP2D6 genotypes including those with multiple genes . Pharmacogenetics , 9 : 697 – 706 .
   PubMedGoogle Scholar
• Daly , A. K. , Brockmoller , J. , Broly , F. , Eichelbaum , M. , Evans , W. E. , Gonzalez , F. J. , Huang , J. D. , Idle , J. R. , Ingelman-Sundberg , M. , Ishizaki , T. , Jacqz-Aigrain , E. , Meyer , U. A. , Nebert , D. W. , Steen , V. M. , Wolf , C. R. and Zanger , U. M. 1996 . Nomenclature for human CYP2D6 alleles . Pharmacogenetics , 6 : 193 – 201 .
   PubMedGoogle Scholar
• Daniels , J. , Williams , J. , Asherson , P. , McGuffin , P. and Owen , M. 1995 . No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT) . Am. J. Med. Genet. , 60 : 85 – 87 .
   PubMed Web of Science ®Google Scholar
• Dayer , P. , Desmeules , J. , Leemann , T. and Striberni , R. 1988 . Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI) . Biochem. Biophys. Res. Commun. , 152 : 411 – 416 .
   PubMed Web of Science ®Google Scholar
• de Groot , M. , Bijloo , G. , van Acker , F. , Fonseca-Guerra , C. , Snijders , J. and Vermeulen , N. 1997 . Extension of a predictive substrate model for human cytochrome P4502D6 . Xenobiotica , 27 : 357 – 368 .
   PubMed Web of Science ®Google Scholar
• de la Torre , R. , Farre , M. , Ortuno , J. , Mas , M. , Brenneisen , R. , Roset , P. , Segura , J. and Cami , J. 2000 . Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans . Br. J. Clin. Pharmacol. , 49 : 104 – 109 .
   PubMed Web of Science ®Google Scholar
• den Dunnen , J. T. and Antonarakis , S. E. 2001 . Nomenclature for the description of human sequence variations . Hum. Genet. , 109 : 121 – 124 .
   PubMed Web of Science ®Google Scholar
• Dong , H. , Haining , R. L. , Thummel , K. E. , Rettie , A. E. and Nelson , S. D. 2000 . Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen . Drug Metab. Dispos. , 28 : 1397 – 4000 .
   PubMed Web of Science ®Google Scholar
• Elbaz , A. , Levecque , C. , Clavel , J. , Vidal , JS. , Richard , F. , Amouyel , P. , Alperovitch , A. , Chartier-Harlin , M. C. and Tzourio , C. 2004 . CYP2D6 polymorphism, pesticide exposure, and Parkinson's disease . Ann. Neurol. , 55 : 430 – 434 .
   PubMed Web of Science ®Google Scholar
• Evans , W. and Relling , M. 1991 . Concordance of P450 2D6 (debrisoquine hydroxylase) phenotype and genotype: inability of dextromethorphan metabolic ration to discriminate reliably heterozygous and homozygous extensive metabolizers . Pharmacogenetics , 1 : 143 – 148 .
   PubMedGoogle Scholar
• Evans , W. E. , Relling , M. V. , Rahman , A. , McLeod , H. L. , Scott , E. P. and Lin , J. 1993 . Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans . J. Clin. Invest. , 91 : 2150 – 2154 .
   PubMed Web of Science ®Google Scholar
• Febbo , P. G. , Kantoff , P. W. , Giovannucci , E. , Brown , M. , Chang , G. , Hennekens , C. H. and Stampfer , M. 1998 . Debrisoquine hydroxylase (CYP2D6) and prostate cancer. Cancer epidemiology, biomarkers and prevention . Am. Assoc. Cancer , 7 : 1075 – 1078 .
   Google Scholar
• Fleming , C. , Kaisary , A. , Wilkinson , G. , Smith , P. and Branch , R. 1992 . The ability to 4-hydroxylate debrisoquine is related to recurrence of bladder cancer . Pharmacogenetics , 2 : 128 – 134 .
   PubMedGoogle Scholar
• Gaedigk , A. , Bhathena , A. , Ndjountche , L. , Pearce , R. E. , Abdel-Rahman , S. M. , Alander , S. W. , Bradford , L, D. , Rogan , P. K. and Leeder , J. S. 2005 . Identification and characterization of novel sequence variations in the cytochrome P4502D6 gene in African-Americans . Pharmacogenom. J , 5 : 173 – 182 .
   PubMed Web of Science ®Google Scholar
• Gaedigk , A. , Bradford , L. D. , Alander , S. W. and Leeder , J. S. 2006 . CYP2D6∗36 gene arrangements within the CYP2D6 locus: Association of CYP2D6∗36 with poor metabolizer status . Drug Metab. Dispos. , 34 : 563 – 569 .
   PubMed Web of Science ®Google Scholar
• Garcia-Barcelo , M. , Chow , L. Y. , Chiu , H. F. , Wing , Y. K. , Lee , D. T. , Lam , K. L. and Waye , M. M. 2000 . Genetic analysis of the CYP2D6 locus in Hong Kong Chinese population . Clin. Chem. , 46 : 18 – 23 .
   PubMed Web of Science ®Google Scholar
• Garte , S. , Gaspari , L. , Alexandrie , A. and Ambrosone , C. 2001 . Metabolic gene polymorphism frequencies in control populations . Cancer Epidemiol. Biomarkers Prev. , 10 : 1239 – 1248 .
   PubMed Web of Science ®Google Scholar
• George , J. , Byth , K. and Farrell , G. 1995 . Age but not gender selectively affects expression of individual cytochrome P450 proteins in human liver . Biochem. Pharmacol. , 50 : 727 – 730 .
   PubMed Web of Science ®Google Scholar
• Gilham , D. , Cairns , W. , Paine , M. , Modi , S. , Poulsom , R. , Roberts , G. and Wolf , C . 1997 . Metabolism of MPTP by cytochrome P4502D6 and the demonstration of 2D6 mRNA in human foetal and adult brain by in situ hybridization . Xenobiotica , 27 : 111 – 125 .
   PubMed Web of Science ®Google Scholar
• Goetz , M. P. , Rae , J. M. , Suman , V. J. , Safgren , S. L. , Ames , M. M. , Visscher , D. W. , Reynolds , C. , Couch , F. J. , Lingle , W. L. , Flockhart , D. A. , Desta , Z. , Perez , E. A. and Ingle , J. N. 2005 . Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes . J. Clin. Oncol. , 23 : 9312 – 9318 .
   PubMed Web of Science ®Google Scholar
• Griese , E. , Zanger , U. M. , Brudermanns , U. , Gaedigk , A. , Mikus , G. , Morike , K. , Stuven , T. and Eichelbaum , M. 1998 . Assessment of the predictive power of genotypes for the in-vivo catalytic function of CYP2D6 in a German population . Pharmacogenetics , 8 : 15 – 26 .
   PubMedGoogle Scholar
• Harhangi , B. , Oostra , B. , Heutink , P. , van Duijn , C. , Hofman , A. and Breteler , M. 2001 . CYP2D6 polymorphism in Parkinson's disease: The Rotterdam Study . Movement Disorders , 16 : 290 – 293 .
   PubMed Web of Science ®Google Scholar
• He , N. , Daniel , H. I. , Hajiloo , L. and Shockley , D. 1999 . Dextromethorphan O-demethylation polymorphism in an African-American population . Eur. J. Clin. Pharmacol. , 55 : 457 – 459 .
   PubMed Web of Science ®Google Scholar
• Hecht , S. 1996 . Recent studies on mechanisms of bioactivation and detoxification of 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific lung carcinogen . Crit. Rev. Toxicol. , 26 : 163 – 181 .
   PubMed Web of Science ®Google Scholar
• Hedenmalm , K. , Lindh , J. D. , Sawe , J. and Rane , A. 2004 . Increased liability of tramadol-warfarin interaction in individuals with mutations in the cytochrome P450 2D6 gene . Eur. J. Clin. Pharmacol. , 60 : 369 – 372 .
   PubMedGoogle Scholar
• Herraiz , T. , Guillen , H. , Aran , V. J. , Idle , J. R. and Gonzalez , F. J. 2006 . Comparative aromatic hydroxylation and N-demethylation of MPTP neurotoxin and its analogs, N-methylated beta-carboline and isoquinoline alkaloids, by human cytochrome P450 2D6 . Toxicol. Appl. Pharmacol. , 216 : 387 – 398 .
   PubMed Web of Science ®Google Scholar
• Hetzel , M. R. , Law , M. , Keal , E. E. , Sloan , T. P. , Idle , J. R. and Smith , R. L. 1980 . Is there a genetic component in bronchial carcinoma in smokers? . Thorax , 35 : 709
   Google Scholar
• Hiroi , T. , Imaoka , S. and Funae , Y. 1998 . Dopamine formation from tyramine by CYP2D6 . Biochem. Biophys. Res. Commun. , 249 : 838 – 843 .
   PubMed Web of Science ®Google Scholar
• Hoffmannn , D. and Hoffmann , I. 1997 . The changing cigarette, 1950–1995 . J. Toxicol. Environ. Health , 50 : 307 – 364 .
   PubMed Web of Science ®Google Scholar
• Idle , J. R. , Armstrong , M. , Boddy , A. V. , Boustead , C. , Cholerton , S. , Cooper , J. , Daly , A. K. , Ellis , J. , Gregory , W. and Hadidi , H. 1992 . The pharmacogenetics of chemical carcinogenesis . Pharmacogenetics , 2 : 246 – 258 .
   PubMedGoogle Scholar
• Ikenaga , Y. , Fukuda , T. , Fukuda , K. , Nishida , Y. , Naohara , M. , Maune , H. and 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 Metab. Pharmacokinet. , 20 : 113 – 116 .
   PubMedGoogle Scholar
• Ingelman-Sundberg , M. 2005 . Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity . Pharmacogenom. J. , 5 : 6 – 13 .
   PubMed Web of Science ®Google Scholar
• Isaza , C. A. , Henao , J. , Lopez , A. M. and Cacabelos , R. 2000 . Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the Columbian population . Methods Findings Exp. Clin. Pharmacol. , 22 : 695 – 705 .
   PubMed Web of Science ®Google Scholar
• Islam , S. , Wolf , C. , Lennard , M. and Sternberg , M. 1991 . A three-dimensional molecular template for substrates of human cytochrome P450 involved in debrisoquine 4-hydroxlation . Carcinogenesis , 12 : 2211 – 2219 .
   PubMed Web of Science ®Google Scholar
• Jacqz-Aigrain , E. and Cresteil , T. 1992 . Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies . Dev. Pharmacol. Ther. , 18 : 161 – 168 .
   PubMedGoogle Scholar
• Johansson , I. , Yue , Q. Y. , Dahl , M. L. , Heim , M. , Sawe , J. , Bertilsson , L. , Meyer , U. A. , Sjoqvist , F. and Ingelman-Sundber , M. 1994 . Genetic analysis of the Chinese cytochrome P4502D locus: Characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation . Mol. Pharmacol. , 46 : 452 – 459 .
   PubMed Web of Science ®Google Scholar
• Jonsson , E. , Dahl , M. , Roh , H. , Jerling , M. and Sedvall , G. 1998 . Lack of association between debrisoquine 4-hydroxylase (CYP2D6) gene polymorphism and schizophrenia . Psychiat. Genet. , 8 : 25 – 28 .
   PubMedGoogle Scholar
• Joost , O. , Taylor , C. A. , Thomas , C. A. , Cupples , L. A. , Saint-Hilaire , M. H. , Feldman , R. G. , Baldwin , C. T. and Myers , R. H. 1999 . Absence of effect of seven functional mutations in the CYP2D6 gene in Parkinson's disease . Movement Disorders , 14 : 590 – 595 .
   PubMed Web of Science ®Google Scholar
• Jorge , L. , Eichelbaum , M. , Griese , E. , Inaba , T. and Arias , T. 1999 . Comparative evolutionary pharmacogenetics of CYP2D6 in Ngawbe and Embera Amerindians of Panama and Colombia: role of selection versus drift in world populations . Pharmacogenetics , 9 : 217 – 228 .
   PubMedGoogle Scholar
• Jurima-Romet , M. , Foster , BC. , Rode , A. , Casley , W. L. , Vloshinsky , P. , Huang , H. S. and Geersten , S. 1997 . CYP2D6-related oxidation polymorphism in a Canadian Inuit population . Can. J. Physiol. Pharmacol. , 75 : 165 – 172 .
   PubMed Web of Science ®Google Scholar
• Kagimoto , M. , Heim , M. , Kagimoto , K. , Zeugin , T. and 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 . J. Biol. Chem. , 265 : 17209 – 17214 .
   PubMed Web of Science ®Google Scholar
• Kaisary , A. , Smith , P. , Jaczq , E. , McAllister , C. , Wilkinson , G. , Ray , W. and Branch , R. 1987 . Genetic predisposition to bladder cancer: Ability to hydroxylate debrisoquine and mephenytoin as risk factors . Cancer Res. , 47 : 5488 – 5493 .
   PubMed Web of Science ®Google Scholar
• Kato , S. , Bowmann , E. D. , Harrington , A. M. , Blomeke , B. and Shields , P. G. 1995 . Human lung carcinogen–DNA adduct levels mediated by genetic polymorphisms in vivo . JNCI , 87 : 902 – 907 .
   PubMed Web of Science ®Google Scholar
• Kimiskidis , V. K. , Niopas , I. , Firinidis , P. D. , Kanaze , F. I. , Gabrieli , C. , Kazis , D. and Papagiannopoulos , S. 2005 . Frequency distribution of dextromethorphan O-demethylation in a Greek population . Int. J. Clin. Pharmacol. Ther. , 43 : 150 – 153 .
   PubMed Web of Science ®Google Scholar
• Kirchheiner , J. , Schmidt , H. , Tzvetkov , M. , Keulen , JT. , Lotsch , J. , Roots , I. and Brockmoller , J. 2006 . Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication . Pharmacogenom. J. , 7 : 257 – 265 .
   PubMed Web of Science ®Google Scholar
• Kubota , T. , Yamaura , Y. , Ohkawa , N. , Hara , H. and Chiba , K. 2000 . Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes . Br. J. Clin. Pharmacol. , 50 : 31 – 34 .
   PubMed Web of Science ®Google Scholar
• Law , M. R. , Hetzel , M. R. and Idle , J. R. 1989 . Debrisoquine metabolism and genetic predisopsition to lung cancer . Br. J. Cancer , 59 : 686 – 687 .
   PubMed Web of Science ®Google Scholar
• Leathart , J. , London , S. J. , Steward , A. , Adams , J. D. , Idle , J. R. and Daly , A. K. 1998 . CYP2D6 phenotype–genotype relationships in African-Americans and Caucasians in Los Angeles . Pharmacogenetics , 8 : 529 – 541 .
   PubMedGoogle Scholar
• Lee , S. , Jang , I. , Shin , S. , Lee , K. , Yim , D. , Kim , S. , Oh , S. and Lee , S. 1994 . CYP1A2 activity as a risk factor for bladder cancer . J. Korean Med. Sci. , 9 : 482 – 489 .
   PubMedGoogle Scholar
• Lee , S. Y. , Sohn , K. M. , Ryu , J. Y. , Yoon , Y. R. , Shin , J. G. and Kim , J. W. 2006 . Sequence-based CYP2D6 genotyping in the Korean population . Ther. Drug Monit. , 28 : 382 – 387 .
   PubMed Web of Science ®Google Scholar
• Le Marchand , L. , Sivaraman , L. , Pierce , L. , Seifried , A. , Lum , A. , Wilkens , L. R. and Lau , A. 1998 . Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities tobacco carcinogens . Cancer Res. , 58 : 4858 – 4863 .
   PubMed Web of Science ®Google Scholar
• Lewis , D. F. V. 1996 . Cytochomes P450: Structure, functions and mechanism , London : Taylor & Francis .
   Google Scholar
• Li , H. , Feng , L. , Xu , Y. , Yao , L. , Quyang , T. , Li , J. , Want , T. , Fan , Z. , Lin , B. and Li , J. 2006 . The association of CYP2D6∗10 polymorphism with breast cancer risk and clinico-pathologic characteristics in Chinese women . Acta Oncol. , 45 : 597 – 601 .
   PubMed Web of Science ®Google Scholar
• London , S. J. , Daly , A. K. , Leathart , J. B. S. , Navidi , W. C. , Carpenter , C. C. and Idle , J. R. 1997 . Genetic polymorphism of CYP2D6 and lung cancer risk in African-Americans and Caucasians in Los Angeles County . Carcinogenesis , 18 : 1203 – 1214 .
   PubMed Web of Science ®Google Scholar
• Lyun , A. O. , Lennari , M. S. , Tucker , G. T. and Woods , H. F. 1986 . Metoprolol and debrisoquin metabolism in Nigerians: Lack of evidence for polymorphic oxidation . Clin. Pharmacol. Ther. , 40 : 387 – 399 .
   PubMedGoogle Scholar
• Mahgoub , A. , Idle , JR. , Dring , LG. , Lancaster , R. and Smith , R. L. 1977 . Polymorphic hydroxylation of debrisoquine in man . Lancet , 2 : 584 – 586 .
   PubMed Web of Science ®Google Scholar
• Marandi , T. , Dahl , M. L. , Rago , L. , Kiivet , R. and Sjoqvist , F. 1997 . Debrisoquine and S-mephenytoin hydroxylation polymorphisms in a Russian population living in Estonia . Eur. J. Clin. Pharmacol. , 53 : 257 – 260 .
   PubMed Web of Science ®Google Scholar
• Marinac , J. S. , Foxworth , J. W. and Willsie , S. K. 1995 . Dextromethorphan polymorphic hepatic oxidation (CYP2D6) in health Black American adult subjects . Ther. Drug Monitor. , 17 : 120 – 124 .
   PubMed Web of Science ®Google Scholar
• Marez , D. , Legrand , M. , Sabbagh , N. , Lo Guidice , J. M , Spire , C. , Lafitte , J. J. , Meyer , U. A. and 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
• Masimirembwa , C. , Hasler , J. , Bertilssons , L. , Johansson , I. , Ekberg , O. and Ingelman-Sundberg , M. 1996 . Pheontype and genotype analysis of debrisoquine hydroxylase (CYP2D6) in a black Zimbabwean population. Reduced enzyme activity and evaluation of metabolic correlation of CYP2D6 probe drugs . Eur. J. Clin. Pharmacol. , 51 : 117 – 122 .
   PubMed Web of Science ®Google Scholar
• McFee , R. , Mofenson , H. and Caraccio , T. 2000 . Dextromethorphan: Another “Ecstasy”? . Arch. Intern. Med. , 9 : 123
   Google Scholar
• McLellan , R. A. , Oscarson , M. , Seidegard , J. , Evans , D. and Ingelman-Sundberg , M. 1997 . Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians . Pharmacogenetics , 7 : 187 – 191 .
   PubMedGoogle Scholar
• Messina , E. S. , Tyndale , R. F. and Sellers , E. M. 1997 . A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes . J. Pharmacol. Exp. Ther. , 282 : 1608 – 1614 .
   PubMed Web of Science ®Google Scholar
• Miller , G. P. , Hanna , I. H. , Nishimura , Y. and Guengerich , F. P. 2001 . Oxidation of phenethylamine derivatives by cytochrome P450 2D6: The issue of substrate protonation in binding and catalysts . Biochemistry , 40 : 14215 – 14223 .
   PubMed Web of Science ®Google Scholar
• Modi , S. , Gilham , D. , Sutcliffe , M. , Lian , L. , Primrose , W. , Wolf , C. and Roberts , G. 1997 . 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase . Biochemistry , 36 : 4461 – 4470 .
   PubMed Web of Science ®Google Scholar
• Munoz , S. , Vollrath , V. , Vallejos , M. , Miquel , J. , Covarrubias , C. and Raddatz , A. 1998 . Genetic polymorphisms of CYP2D6, CYP1A1 and CYP2E1 in the South-Amerindian population of Chile . Pharmacogenetics , 8 : 343 – 351 .
   PubMedGoogle Scholar
• Naveen , A. T. , Adithan , C. , Soya , S. S. , Gerard , N. and Krishnamoorthy , R. 2006 . CYP2D6 genetic polymorphism in South Indian populations . Biol. Pharm. Bull. , 29 : 1655 – 1658 .
   PubMed Web of Science ®Google Scholar
• Nebert , D. W. 1991 . Polymorphism of human CYP2D genes involved in drug metabolism possible relationship to individual cancer risk . Cancer Cell , 3 : 93 – 96 .
   Google Scholar
• Nebert , D. W. , McKinnon , R. A. and Puga , A. 1996 . Human drug-metabolizing enzyme polymorphisms: Effects on risk of toxicity and cancer . DNA Cell Biol. , 15 : 273 – 280 .
   PubMed Web of Science ®Google Scholar
• Nowak , M. P. , Tyndale , R. F. and Sellers , E. M. 1997 . CYP2D6 phenotype and genotype in a Canadian native Indian population . Pharmacogenetics , 7 : 145 – 148 .
   PubMedGoogle Scholar
• Oscarson , M. , Hidestrand , M. , Johansson , I. and Ingelman-Sundberg , M. 1997 . A combination of mutations in the CYP2D6∗17 (CYP2D6Z) allele causes alterations in enzyme function . Mol. Pharmacol. , 52 : 1034 – 1040 .
   PubMed Web of Science ®Google Scholar
• Oscarson , M. , Gullsten , H. , Rautio , A. , Bernal , ML. , Sinues , B. , Dahl , M. , Stengård , J. H. , Pelkonen , O. , Raunio , H. and Ingelman-Sundberg , M. 1998 . Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase . FEBS Lett. , 438 : 201 – 205 .
   PubMed Web of Science ®Google Scholar
• Patten , C. , Smith , T. , Murphy , S. , Wang , M. , Lee , J. , Tynes , R. , Koch , P. and Yang , C. 1996 . Kinetic analysis of the activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by heterologously expressed human P450 enzymes and the effect of P450-specific chemical inhibitors on this activation in human liver microsomes . Arch. Biochem. Biophys. , 333 : 127 – 138 .
   PubMed Web of Science ®Google Scholar
• Payami , H. , Lee , N. , Zareparsi , S. , Gonzales-McNeal , M. , Camicioli , R. , Bird , T. , Sexton , G. , Gancher , S. , Kay , J. , Calhoun , D. , Swanson , P. and Nutt , J. 2001 . Parkinson's disease, CYP2D6 polymorphism and age . Neurology , 56 : 1363 – 1370 .
   PubMed Web of Science ®Google Scholar
• Pedersen , R. S. , Damkier , P. and Brosen , K. 2005 . Tramadol as a new probe for cytochrome P450 2D6 phenotyping: A population study . Clin. Pharmacol. Ther. , 77 : 458 – 467 .
   PubMed Web of Science ®Google Scholar
• Pianezza , M. L. , Sellers , E. M. and Tyndale , R. F. 1998 . Nicotine metabolism defect reduces smoking . Nature , 393 : 750
   PubMed Web of Science ®Google Scholar
• Raimundo , S. , Toscano , C. , Klein , K. , Griese , E. U. , Eichelbaum , M. , Schwab , M. and Zanger , U. M. 2004 . A novel intronic mutation, 2988G>A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects . Clin. Pharmacol. Ther. , 76 : 128 – 138 .
   PubMed Web of Science ®Google Scholar
• Ramamoorthy , Y. , Tyndale , R. and Sellers , E. 2001 . Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates . Pharmacogenetics , 11 : 477 – 487 .
   PubMedGoogle Scholar
• Rasmussen , J. O. , Christensen , M. , Svendsen , J. M. , Skausig , O. , Hansen , E. L. and Nielsen , K. A. 2006 . CYP2D6 gene test in psychiatric patients and healthy volunteers . Scand. J. Clin. Lab. Invest. , 66 : 129 – 136 .
   PubMed Web of Science ®Google Scholar
• Relling , M. V. , Cherrie , J. , Schell , M. J. , Petros , W. P. , Meyer , W. H. and Evans , W. E. 1991 . Lower prevalence of the debrisoquin oxidative poor metabolizer phenotype in American black versus white subjects . Clin. Pharmacol. Ther. , 50 : 308 – 313 .
   PubMed Web of Science ®Google Scholar
• Roh , H. K. , Dahl , M. , Johansson , I. , Ingelman-Sundberg , M. , Cha , Y. and Bertilsson , L. 1996 . Debrisoquine and s-mephenytoin hydroxylation phenotypes and genotypes in a Korean population . Pharmacogenetics , 6 : 441 – 447 .
   PubMedGoogle Scholar
• Romkes-Sparks , M. , Mnuskin , A. , Chern , H. , Persad , R. , Fleming , C. , Sibley , G. N. , Smith , P. , Wilkinson , G. R. and Branch , R. A. 1994 . Correlation of polymorphic expression of CYP2D6 mRNA in bladder mucosa and tumor tissue to in vivo debrisoquine hydroxylase activity . Carcinogenesis , 15 : 1955 – 1961 .
   PubMed Web of Science ®Google Scholar
• Romkes , M. , Chern , H. , Lesnick , T. , Becich , M. , Persad , R. , Smith , P. and Branch , R. 1996 . Association of low CYP3A activity with p53 mutation and CYP2D6 activity with Rb mutation in human bladder cancer . Carcinogenesis , 17 : 1057 – 1062 .
   PubMedGoogle Scholar
• Rostami-Hodjegan , A. , Lennard , M. S. , Woods , H. F. and Tucker , G. T. 1998 . Meta-analysis of studies of the CYP2D6 polymorphism in relation to lung cancer and Parkinson's disease . Pharmacogenetics , 8 : 227 – 238 .
   PubMedGoogle Scholar
• Rumack , B. H. and Peterson , R. G. 1978 . Acetaminophen overdose: incidence, diagnosis and management in 416 patients . Pediatrics , 62 : 898 – 903 .
   PubMed Web of Science ®Google Scholar
• Saarikoski , ST. , Sata , F. , Husgafvel-Pursiainen , K. , Rautalahti , M. , Haukka , J. , Impivaara , O. , Jarvisalo , J. , Vainio , H. and Hirvonen , A. 2000 . CYP2D6 ultrarapid metabolizer genotype as a potential modifier of smoking behavior . Pharmacogenetics , 10 : 5 – 10 .
   PubMedGoogle Scholar
• Sabbagh , N. , Brice , A. , Marez , D. , Durr , A. , Legrand , M. , Lo-Guidice , J. , Destee , A. , Agid , Y. and Broly , F. 1999 . CYP2D6 polymorphism and Parkinson's disease susceptibility . Movement Disorders , 14 : 230 – 236 .
   PubMed Web of Science ®Google Scholar
• Sachse , C. , Brockmoller , J. , Bauer , S. and Roots , I. 1997 . Cytochrome P4502D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences . Am. J. Hum. Genet. , 60 : 284 – 295 .
   PubMed Web of Science ®Google Scholar
• Sachse , C. , Brockmoller , J. , Hildebrand , M. , Muller , K. and 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
• Sams , C. , Mason , H. J. and Rawbone , R. 2000 . Evidence for the activation or organophosphate pesticides by cytochromes P450 3A4 and 2D6 in human liver microsomes . Toxicol. Lett. , 116 : 217 – 221 .
   PubMed Web of Science ®Google Scholar
• Segura , M. , Farre , M. , Pichini , S. , Peiro , A. M. , Roset , P. N. , Ramirez , A. , Ortuno , J. , Pacifici , R. , Zuccaro , P. , Segura , J. and de la Torre , R. 2005 . Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: Use of paroxetine as a metabolic inhibitor probe . Clin. Pharmacokinet. , 44 : 649 – 660 .
   PubMed Web of Science ®Google Scholar
• Shams , M. E. , Arneth , B. , Hiemke , C. , Dragicevic , A. , Muller , M. J. , Kaiser , R. , Lackner , K. and Hartter , S. 2006 . CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine . J. Clin. Pharm. Ther. , 31 : 493 – 502 .
   PubMed Web of Science ®Google Scholar
• Shimada , T. , Yamazaki , H. , Mimura , M. , Inui , Y. and Guengerich , F. 1994 . Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians . J. Pharmacol.Exp.Ther. , 270 : 414 – 423 .
   PubMed Web of Science ®Google Scholar
• Shows , T. B. , McAlpine , P. J. , Boucheix , C. , Collins , F. S. , Conneally , P. M. , Frezal , J. , Gershowitz , H. , Goodfellow , P. N. , Hall , J. G. , Issitt , P. , Jones , C. A. , Knowles , B. B. , Lewis , M. , McKusick , V. A. , Meisler , M. , Morton , N. E. , Rubenstein , P. , Schanfield , M. S. , Schmickel , R. D. , Skolnick , M. H. , Spence , M. A. , Sutherland , G. R. , Traver , M. , Vancong , N. and Willard , H. F. 1987 . Guidelines for human gene nomenclature. An international system for human gene nomenclature . Cytogenet. Cell Genet. , l46 : 11 – 28 .
   Google Scholar
• Simooya , O. , Njunju , E. and Hodjegan , A. R. 1993 . Debrisoquin and metoprolol oxidation in Zambians: A population study . Pharmacogenetics , 3 : 205 – 208 .
   PubMedGoogle Scholar
• Smith , D. A. , Abel , S. M. , Hyland , R. and Jones , B. C. 1998 . Human cytochrome P450s: selectivity and measurement in vivo . Xenobiotica , 28 : 1095 – 1128 .
   PubMed Web of Science ®Google Scholar
• Sommers , D. K. , Monerieff , J. and Avenant , J. 1988 . Polymorphism of the 4-hydroxylation of debrisoquin in the San Bushmen of Southern Africa . Hum. Toxicol. , 7 : 273 – 276 .
   PubMedGoogle Scholar
• Sosa-Macias , M. , Elizondo , G. , Flores-Perez , C. , Flores-Perez , J. , Bradley-Alvarez , F. , Alanos-Banuelos , R. E. and Lares-Asseff , I. 2006 . CYP2D6 genotype and phenotype in Amerindians of Tepehuano origin and Mestizos of Durango, Mexico . J. Clin. Pharmacol. , 46 : 527 – 536 .
   PubMed Web of Science ®Google Scholar
• Soyama , A. , Saito , Y. , Miyajima , A. , Ohno , Y. , Komamura , K. , Ueno , K. , Kamakura , S. , Kitakaze , M. , Tomoike , H. , Ozawa , S. and Sawada , J. 2006 . Sequence-based analysis of the CYP2D6∗36-CYP2D6∗10 tandem-type arrangement, a major CYP2D6∗10 haplotype in the Japanese population . Drug Metab. Pharmacokinet. , 21 : 208 – 216 .
   PubMed Web of Science ®Google Scholar
• Stefanovic , M. , Topic , E. , Ivanisevic , A. , Relja , M. and Korsic , M. 2000 . Genotyping of CYP2D6 in Parkinson's disease . Clin. Chem. Lab. Med. , 38 : 929 – 934 .
   PubMed Web of Science ®Google Scholar
• Tanaka , E. 1998 . In vivo age-related changes in hepatic drug-oxidizing capacity in humans . J. Clin. Pharm. Ther. , 23 : 247 – 255 .
   PubMed Web of Science ®Google Scholar
• Taningher , M. , Malacarne , D. , Izzotti , A. , Ugolini , D. and Parodi , S. 1999 . Drug metabolism polymorphisms as modulators of cancer susceptibility . Mutat. Res. , 436 : 227 – 261 .
   PubMed Web of Science ®Google Scholar
• Tateishi , T. , Chida , M. , Ariyoshi , N. , Mizorogi , Y. , Kamataki , T. and Kobayashi , S. 1999 . Analysis of the CYP2D6 gene in relation to destromethorphan O-demethylation capacity in a Japanese population . Clin. Pharmacol. Ther. , 65 : 570 – 575 .
   PubMed Web of Science ®Google Scholar
• Thuerauf , N. and Lunkenheimer , J. 2006 . The impact of the CYP2D6-polymorphism on dose recommendations for current antidepressants . Eur. Arch. Psychiat. Clin. Neurosci. , 256 : 287 – 293 .
   PubMedGoogle Scholar
• Toscano , C. , Klein , K. , Blievernicht , J. , Schaeffeler , E. , Saussele , T. , Raimundo , S. , Eichelbaum , M. , Schwab , M. and Zanger , UM. 2006a . Impaired expression of CYP2D6 in intermediate metabolizers carrying the ∗41 allele caused by the intronic SNP 2988G>A: Evidence for modulation of splicing events . Pharmacogenet. Genom. , 16 : 755 – 766 .
   PubMed Web of Science ®Google Scholar
• Toscano , C. , Raimundo , S. , Klein , K. , Eichelbaum , M. , Schwab , M. and Zanger , U. M. 2006b . A silent mutation (2939G>A, exon 6; CYP2D6∗59) leading to impaired expression and function of CYP2D6 . Pharmacogenet. Genom. , 16 : 767 – 770 .
   PubMed Web of Science ®Google Scholar
• Vandel , P. , Haffen , E. , Vandel , S. , Bonin , B. , Nezelof , S. , Sechter , D. , Broly , F. , Bizouard , P. and Dalery , J. 1999 . Drug extrapyramidal side effects. CYP2D6 genotypes and phenotypes . Eur. J. Clin. Pharmacol. , 55 : 659 – 665 .
   PubMed Web of Science ®Google Scholar
• Vincent-Viry , M. , Fournier , B. and Galteau , M. M. 2000 . The effects of drinking and smoking on the CYP2D6 metabolic capacity . Drug Metab. Dispos. , 28 : 617 – 619 .
   PubMed Web of Science ®Google Scholar
• Wadelius , M. , Autrup , J. , Stubbins , M. , Andersson , S. , Johansson , J. , Wadelius , C. , Wolf , C. , Autrup , H. and Rane , A. 1999 . Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer . Pharmacogenetics , 9 : 333 – 340 .
   PubMedGoogle Scholar
• Wang , S. L. , Huang , J. D. , Lai , M. D. , Liu , B. H. and Lai , M. L. 1993 . Molecular basis of genetic variation in debrisoquine hydroxylation in Chinese subjects: Polymorphism in RFLP an DNA sequence of CYP2D6 . Clin. Pharmacol. Ther. , 53 : 410 – 418 .
   PubMed Web of Science ®Google Scholar
• Wang , S. , Lai , M. and Huang , J. 1999 . G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese . Drug Metab. Dispos. , 27 : 385 – 388 .
   PubMed Web of Science ®Google Scholar
• Wang , G. , Zhang , H. , He , F. , Fang , X. , Wang , S. , Lai , M. and Huang , J. 2006 . Effect of the CYP2D6∗10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population . Eur. J. Clin. Pharmacol. , 62 : 927 – 931 .
   PubMed Web of Science ®Google Scholar
• Woolhouse , N. M. , Andoh , B. and Mahgoub , A. 1979 . Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians . Clin. Pharmacol. Ther. , 26 : 584 – 591 .
   PubMed Web of Science ®Google Scholar
• Woolhouse , N. M. , Eichelbaum , M. and Oates , N. S. 1985 . Dissociation of co-regulatory control of debrisoquin/phenformin and sparteine oxidation in Ghanaians . Clin. Pharmacol. Ther. , 37 : 512 – 527 .
   PubMed Web of Science ®Google Scholar
• Woolverton , W. L. and Johnson , K. M. 1992 . Neurobiology of cocaine abuse . Trends Pharmacol Sci. , 13 : 193 – 200 .
   PubMed Web of Science ®Google Scholar
• Yamada , H. , Dahl , M. , Lannfelt , L. , Viitanen , M. , Winblad , B. and Sjoqvist , F. 1998 . CYP2D6 and CYP2C19 genotypes in an elderly Swedish population . Eur. J. Clin. Pharmacol. , 54 : 479 – 481 .
   PubMed Web of Science ®Google Scholar
• Yamazaki , H. , Inui , Y. , Yun , C. , Guengerich , F.. and Shimada , T. 1992 . Cytrochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes . Carcinogenesis , 13 : 1789 – 1794 .
   PubMed Web of Science ®Google Scholar
• Yamazaki , H. , Kiyotani , K. , Tsubuko , S. , Matsunaga , M. , Miura , J. , Kobayashi , S. , Kamataki , T. , Fujieda , M. and Saito , T. 2003 . Two novel haplotypes of CYP2D6 gene in a Japanese population . Drug Metab. Pharmacokinet. , 18 : 269 – 271 .
   PubMedGoogle Scholar
• Yang , C. S. and Smith , T. J. 1996 . Mechanisms of nitrosamine bioactivation and carcinogenesis . Adv. Exp. Med. Biol. , 387 : 385 – 394 .
   PubMedGoogle Scholar
• Yokoi , T. , Kosaka , Y. , Chida , M. , Chiba , K. , Nakamura , H. , Ishizaki , T. , Kinoshita , M. , Sato , K. , Gonzalez , F. and 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
• Yue , Q. , Zhong , Z. , Tybring , G. , Dalen , P. , Dahl , M. , Bertilsson , L. and Sjoqvist , F. 1998 . Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes . Clin. Pharmacol. Ther. , 64 : 384 – 390 .
   PubMed Web of Science ®Google Scholar
• Zanger , U. M. , Raimundo , S. and Eichelbaum , M. 2004 . Cytochrome P450 2D6: Overview and update on pharmacology, genetics, biochemistry . Naunyn Schmiedebergs Arch. Pharmakol. , 369 : 23 – 37 .
   PubMed Web of Science ®Google Scholar