1,023
Views
123
CrossRef citations to date
0
Altmetric
Reviews

Interethnic variability of CYP2D6 alleles and of predicted and measured metabolic phenotypes across world populations

, , , , &

Bibliography

  • Ingelman-Sundberg M. Genetic polymorphisms of cytochrome. P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005;5:6-13
  • The human cytocrome P450 (CYP) allele nomenclature database [Internet]. 2014. Available from: www.cypalleles.ki.se/ [Cited 15 April 2014]
  • Gaedigk A. Complexities of CYP2D6 gene analysis and interpretation. Int Rev Psychiatry 2013;25:534-53
  • Llerena A, Dorado P, Penas-Lledo EM. Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics 2009;10:17-28
  • LLerena A, Berecz R, de la Rubia A, Dorado P. QTc interval lengthening and debrisoquine metabolic ratio in psychiatric patients treated with oral haloperidol monotherapy. Eur J Clin Pharmacol 2002;58:223-4
  • Penas-Lledo EM, Trejo HD, Dorado P, et al. CYP2D6 ultrarapid metabolism and early dropout from fluoxetine or amitriptyline monotherapy treatment in major depressive patients. Mol Psychiatry 2013;18:8-9
  • Berecz R, de la Rubia A, Dorado P, et al. Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype. Eur J Clin Pharmacol 2003;59:45-50
  • LLerena A, de la Rubia A, Berecz R, Dorado P. Relationship between haloperidol plasma concentration, debrisoquine metabolic ratio, CYP2D6 and CYP2C9 genotypes in psychiatric patients. Pharmacopsychiatry 2004;37:69-73
  • Llerena A, Berecz R, Dorado P, de la Rubia A. QTc interval, CYP2D6 and CYP2C9 genotypes and risperidone plasma concentrations. J Psychopharmacol 2004;18:189-93
  • Zackrisson AL, Lindblom B, Ahlner J. High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases. Clin Pharmacol Ther 2010;88:354-9
  • Penas-Lledo EM, Dorado P, Aguera Z, et al. High risk of lifetime history of suicide attempts among CYP2D6 ultrarapid metabolizers with eating disorders. Mol Psychiatry 2011;16:691-2
  • Penas-Lledo EM, Blasco-Fontecilla H, Dorado P, et al. CYP2D6 and the severity of suicide attempts. Pharmacogenomics 2012;13:179-84
  • Ciszkowski C, Madadi P, Phillips MS, et al. Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med 2009;361:827-8
  • Kelly LE, Rieder M, van den Anker J, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics 2012;129:e1343-7
  • Llerena A, Cobaleda J, Martinez C, Benitez J. Interethnic differences in drug metabolism: influence of genetic and environmental factors on debrisoquine hydroxylation phenotype. Eur J Drug Metab Pharmacokinet 1996;21:129-38
  • Sistonen J, Sajantila A, Lao O, et al. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet Genomics 2007;17:93-101
  • Teh LK, Bertilsson L. Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance. Drug Metab Pharmacokinet 2012;27:55-67
  • Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 2014;95:376-82
  • Gaedigk A, Simon SD, Pearce RE, et al. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther 2008;83:234-42
  • Llerena A, Dorado P, Ramirez R, et al. CYP2D6 genotype and debrisoquine hydroxylation phenotype in Cubans and Nicaraguans. Pharmacogenomics J 2012;12:176-83
  • Hicks JK, Swen JJ, Gaedigk A. Challenges in CYP2D6 phenotype assignment from genotype data: a critical assessment and call for standardization. Curr Drug Metab 2014;15:218-32
  • Frank D, Jaehde U, Fuhr U. Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. Eur J Clin Pharmacol 2007;63:321-33
  • GraphPad software [Internet]. 2014. Available from: www.graphpad.com [Cited April 2014]
  • Kohlrausch FB, Gama CS, Lobato MI, et al. Molecular diversity at the CYP2D6 locus in healthy and schizophrenic southern Brazilians. Pharmacogenomics 2009;10:1457-66
  • Wennerholm A, Johansson I, Massele AY, et al. Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype. Pharmacogenetics 1999;9:707-14
  • World population statistics [Internet]. 2014. Available from: www.worldpopulationstatistics.com [Cited 1 May 2014]
  • Penas-Lledo EM, Dorado P, Aguera Z, et al. CYP2D6 polymorphism in patients with eating disorders. Pharmacogenomics J 2012;12:173-5
  • Aklillu E, Persson I, Bertilsson L, et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther 1996;278:441-6
  • Montane Jaime LK, Lalla A, Steimer W, Gaedigk A. Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: discovery of novel allelic variants. Pharmacogenomics 2013;14:261-76
  • Henn BM, Cavalli-Sforza LL, Feldman MW. The great human expansion. Proc Natl Acad Sci USA 2012;109:17758-64
  • Excoffier L, Ray N. Surfing during population expansions promotes genetic revolutions and structuration. Trends Ecol Evol 2008;23:347-51
  • Fuselli S, de Filippo C, Mona S, et al. Evolution of detoxifying systems: the role of environment and population history in shaping genetic diversity at human CYP2D6 locus. Pharmacogenet Genomics 2010;20:485-99
  • Campbell MC, Tishkoff SA. The evolution of human genetic and phenotypic variation in Africa. Curr Biol 2010;20:R166-73
  • Griese EU, Asante-Poku S, Ofori-Adjei D, et al. Analysis of the CYP2D6 gene mutations and their consequences for enzyme function in a West African population. Pharmacogenetics 1999;9:715-23
  • Panserat S, Sica L, Gerard N, et al. CYP2D6 polymorphism in a Gabonese population: contribution of the CYP2D6*2 and CYP2D6*17 alleles to the high prevalence of the intermediate metabolic phenotype. Br J Clin Pharmacol 1999;47:121-4
  • Pagani L, Kivisild T, Tarekegn A, et al. Ethiopian genetic diversity reveals linguistic stratification and complex influences on the Ethiopian gene pool. Am J Hum Genet 2012;91:83-96
  • Dahl ML, Johansson I, Bertilsson L, et al. Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. J Pharmacol Exp Ther 1995;274:516-20
  • Llerena A, Dorado P, Ramirez R, et al. CYP2D6 -1584C>G promoter polymorphism and debrisoquine ultrarapid hydroxylation in healthy volunteers. Pharmacogenomics 2013;14:1973-7
  • 1000 genomes [Internet]. 2014. Available from: www.1000genomes.org/ [Cited 26 June 2014]
  • NHLBI grand opportunity exome sequencing project (ESP) [Internet]. 2014. Available from: https://esp.gs.washington.edu/drupal/ [Cited 26 June 2014]
  • National human genome research institute [Internet]. 2014. Available from: www.genome.gov/encode/ [Cited 26 June 2014]
  • Masimirembwa C, Hasler J, Bertilssons L, et al. Phenotype 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 1996;51:117-22
  • Dodgen TM, Hochfeld WE, Fickl H, et al. Introduction of the AmpliChip CYP450 test to a South African cohort: a platform comparative prospective cohort study. BMC Med Genet 2013;14:20
  • Bathum L, Skjelbo E, Mutabingwa TK, et al. Phenotypes and genotypes for CYP2D6 and CYP2C19 in a black Tanzanian population. Br J Clin Pharmacol 1999;48:395-401
  • Evans WE, Relling MV, Rahman A, et al. Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans. J Clin Invest 1993;91:2150-4
  • Wan YJ, Poland RE, Han G, et al. Analysis of the CYP2D6 gene polymorphism and enzyme activity in African-Americans in southern California. Pharmacogenetics 2001;11:489-99
  • Gaedigk A, Bradford LD, Marcucci KA, Leeder JS. Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans. Clin Pharmacol Ther 2002;72:76-89
  • Maciel ME, Oliveira FK, Propst GB, et al. Population analysis of xenobiotic metabolizing genes in south Brazilian Euro- and Afro-descendants. Genet Mol Biol 2009;32:723-8
  • Kouhi H, Hamzeiy H, Barar J, et al. Frequency of five important CYP2D6 alleles within an Iranian population (eastern Azerbaijan). Genet Test Mol Biomarkers 2009;13:665-70
  • Hashemi-Soteh SM, Sarzare F, Merat F, et al. Frequencies of three CYP2D6 nonfunctional alleles (CYP2D6*3, *4, and *6) within an Iranian population (Mazandaran). Genet Test Mol Biomarkers 2011;15:821-5
  • Luo HR, Aloumanis V, Lin KM, et al. Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups. Am J Pharmacogenomics 2004;4:395-401
  • Zihlif M, Imraish A, Irshaid YM. Frequency of certain single-nucleotide polymorphisms and duplication of CYP2D6 in the Jordanian population. Genet Test Mol Biomarkers 2012;16:1201-5
  • Fuselli S, Dupanloup I, Frigato E, et al. Molecular diversity at the CYP2D6 locus in the Mediterranean region. Eur J Hum Genet 2004;12:916-24
  • Aynacioglu AS, Sachse C, Bozkurt A, et al. Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population. Clin Pharmacol Ther 1999;66:185-92
  • Aydin M, Hatirnaz O, Erensoy N, Ozbek U. CYP2D6 and CYP1A1 mutations in the Turkish population. Cell Biochem Funct 2005;23:133-5
  • Serin A, Canan H, Alper B, Gulmen M. The frequencies of mutated alleles of CYP2D6 gene in a Turkish population. Forensic Sci Int 2012;222:332-4
  • Scott SA, Edelmann L, Kornreich R, et al. CYP2C9, CYP2C19 and CYP2D6 allele frequencies in the Ashkenazi Jewish population. Pharmacogenomics 2007;8:721-30
  • Ismail R, Teh LK. Genetic polymorphism of CYP2D6: malaysian Indians have the highest frequency for CYP2D6*4 in Asia. Eur J Clin Pharmacol 2001;57:617-18
  • Naveen AT, Adithan C, Soya SS, et al. CYP2D6 genetic polymorphism in South Indian populations. Biol Pharm Bull 2006;29:1655-8
  • Adithan C, Gerard N, Naveen AT, et al. Genotype and allele frequency of CYP2D6 in Tamilian population. Eur J Clin Pharmacol 2003;59:517-20
  • Garcia-Barcelo M, Chow LY, Lam KL, et al. Occurrence of CYP2D6 gene duplication in Hong Kong Chinese. Clin Chem 2000;46:1411-13
  • Garcia-Barcelo M, Chow LY, Chiu HF, et al. Genetic analysis of the CYP2D6 locus in a Hong Kong Chinese population. Clin Chem 2000;46:18-23
  • Ji L, Pan S, Marti-Jaun J, et al. Single-step assays to analyze CYP2D6 gene polymorphisms in Asians: allele frequencies and a novel *14B allele in mainland Chinese. Clin Chem 2002;48:983-8
  • Sheng HH, Zeng AP, Zhu WX, et al. Allelic distributions of CYP2D6 gene copy number variation in the eastern Han Chinese population. Acta Pharmacol Sin 2007;28:279-86
  • Qin S, Shen L, Zhang A, et al. Systematic polymorphism analysis of the CYP2D6 gene in four different geographical Han populations in mainland China. Genomics 2008;92:152-8
  • Zhou Q, Yu XM, Lin HB, et al. Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese. Pharmacogenomics J 2009;9:380-94
  • Shi Y, Xiang P, Li L, Shen M. Analysis of 50 SNPs in CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 by MALDI-TOF mass spectrometry in Chinese Han population. Forensic Sci Int 2011;207:183-7
  • Yin SJ, Ni YB, Wang SM, et al. Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations. J Clin Pharm Ther 2012;37:364-9
  • Zuo LJ, Guo T, Xia DY, Jia LH. Allele and genotype frequencies of CYP3A4, CYP2C19, and CYP2D6 in Han, Uighur, Hui, and Mongolian Chinese populations. Genet Test Mol Biomarkers 2012;16:102-8
  • Qian JC, Xu XM, Hu GX, et al. Genetic variations of human CYP2D6 in the Chinese Han population. Pharmacogenomics 2013;14:1731-43
  • Kim EY, Lee SS, Jung HJ, et al. Robust CYP2D6 genotype assay including copy number variation using multiplex single-base extension for Asian populations. Clin Chim Acta 2010;411:2043-8
  • Tateishi T, Chida M, Ariyoshi N, et al. Analysis of the CYP2D6 gene in relation to dextromethorphan O-demethylation capacity in a Japanese population. Clin Pharmacol Ther 1999;65:570-5
  • Nishida Y, Fukuda T, Yamamoto I, Azuma J. CYP2D6 genotypes in a Japanese population: low frequencies of CYP2D6 gene duplication but high frequency of CYP2D6*10. Pharmacogenetics 2000;10:567-70
  • Ishiguro A, Kubota T, Sasaki H, et al. Common mutant alleles of CYP2D6 causing the defect of CYP2D6 enzyme activity in a Japanese population. Br J Clin Pharmacol 2003;55:414-15
  • Ryu SW, Kim YJ, Kim E. Mutation analysis of CYP2D6 locus in the Korean population: identification of rare poor metabolizer alleles at the nucleotide level. Mol Cells 1998;8:758-63
  • Lee SY, Sohn KM, Ryu JY, et al. Sequence-based CYP2D6 genotyping in the Korean population. Ther Drug Monit 2006;28:382-7
  • Lee SJ, Lee SS, Jung HJ, et al. Discovery of novel functional variants and extensive evaluation of CYP2D6 genetic polymorphisms in Koreans. Drug Metab Dispos 2009;37:1464-70
  • Teh LK, Ismail R, Yusoff R, et al. Heterogeneity of the CYP2D6 gene among Malays in Malaysia. J Clin Pharm Ther 2001;26:205-11
  • Ismail R, Teh LK, Amir J, et al. Genetic polymorphism of CYP2D6 in Chinese subjects in Malaysia. J Clin Pharm Ther 2003;28:279-84
  • Veiga MI, Asimus S, Ferreira PE, et al. Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam. Eur J Clin Pharmacol 2009;65:355-63
  • Griese EU, Ilett KF, Kitteringham NR, et al. Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in Aborigines from Western Australia. Pharmacogenetics 2001;11:69-76
  • Lea RA, Roberts RL, Green MR, et al. Allele frequency differences of cytochrome P450 polymorphisms in a sample of New Zealand Maori. N Z Med J 2008;121:33-7
  • Jurima-Romet M, Foster BC, Casley WL, et al. CYP2D6-related oxidation polymorphism in a Canadian Inuit population. Can J Physiol Pharmacol 1997;75:165-72
  • Munoz S, Vollrath V, Vallejos MP, et al. Genetic polymorphisms of CYP2D6, CYP1A1 and CYP2E1 in the South-Amerindian population of Chile. Pharmacogenetics 1998;8:343-51
  • Jorge LF, Eichelbaum M, Griese EU, et al. Comparative evolutionary pharmacogenetics of CYP2D6 in Ngawbe and Embera Amerindians of Panama and Colombia: role of selection versus drift in world populations. Pharmacogenetics 1999;9:217-28
  • Sosa-Macias M, Elizondo G, Flores-Perez C, et al. CYP2D6 genotype and phenotype in Amerindians of Tepehuano origin and Mestizos of Durango. Mexico. J Clin Pharmacol 2006;46:527-36
  • Sosa-Macias M, Dorado P, Alanis-Banuelos RE, et al. Influence of CYP2D6 deletion, multiplication, -1584C->G, 31G->A and 2988G–>a gene polymorphisms on dextromethorphan metabolism among Mexican Tepehuanos and Mestizos. Pharmacology 2010;86:30-6
  • Lazalde-Ramos BP, Martinez-Fierro Mde L, Galaviz-Hernandez C, et al. CYP2D6 gene polymorphisms and predicted phenotypes in eight indigenous groups from northwestern Mexico. Pharmacogenomics 2014;15:339-48
  • Fohner A, Muzquiz LI, Austin MA, et al. Pharmacogenetics in American Indian populations: analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai tribes. Pharmacogenet Genomics 2013;23:403-14
  • Bailliet G, Santos MR, Alfaro EL, et al. Allele and genotype frequencies of metabolic genes in Native Americans from Argentina and Paraguay. Mutat Res 2007;627:171-7
  • Céspedes-Garro C, Jiménez-Arce G, Naranjo MEG, et al. Ethnic background and CYP2D6 genetic polymorphisms in Costa Ricans. Int J Trop Biol Conserv 2014;62:1659-71
  • Griman P, Moran Y, Valero G, et al. CYP2D6 gene variants in urban/admixed and Amerindian populations of Venezuela: pharmacogenetics and anthropological implications. Ann Hum Biol 2012;39:137-42
  • Salazar-Flores J, Torres-Reyes LA, Martinez-Cortes G, et al. Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer phenotype in five Amerindian groups and western Mestizos from Mexico. Genet Test Mol Biomarkers 2012;16:1098-104
  • Isaza CA, Henao J, Lopez AM, Cacabelos R. Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the Colombian population. Methods Find Exp Clin Pharmacol 2000;22:695-705
  • Mendoza R, Wan YJ, Poland RE, et al. CYP2D6 polymorphism in a Mexican American population. Clin Pharmacol Ther 2001;70:552-60
  • Lopez M, Guerrero J, Jung-Cook H, Alonso ME. CYP2D6 genotype and phenotype determination in a Mexican Mestizo population. Eur J Clin Pharmacol 2005;61:749-54
  • Luo HR, Gaedigk A, Aloumanis V, Wan YJ. Identification of CYP2D6 impaired functional alleles in Mexican Americans. Eur J Clin Pharmacol 2005;61:797-802
  • Casner PR. The effect of CYP2D6 polymorphisms on dextromethorphan metabolism in Mexican Americans. J Clin Pharmacol 2005;45:1230-5
  • Contreras AV, Monge-Cazares T, Alfaro-Ruiz L, et al. Resequencing, haplotype construction and identification of novel variants of CYP2D6 in Mexican Mestizos. Pharmacogenomics 2011;12:745-56
  • Orengo-Mercado C, Nieves B, Lopez L, et al. Frequencies of functional polymorphisms in three pharmacokinetic genes of clinical interest within the admixed Puerto Rican population. J Pharmacogenomics Pharmacoproteomics 2013;4:1000113
  • Silveira Vda S, Canalle R, Scrideli CA, et al. Polymorphisms in genes encoding drugs and xenobiotic metabolizing enzymes in a Brazilian population. Biomarkers 2009;14:111-17
  • Roco A, Quinones L, Agundez JA, et al. Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the Chilean population: comparison with Caucasian and Asian populations. Front Genet 2012;3:229
  • Dorado P, Heras N, Machin E, et al. CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population. Eur J Clin Pharmacol 2012;68:637-44
  • Grimán P, Morán Y, Camargo M, Chiurillo MA. Caracterización de variantes alélicas del citocromo CYP2D6 en la población de la región centrooccidental de Venezuela. Acta Biológica Colombiana 2009;14:195-202
  • Gaedigk A, Coetsee C. The CYP2D6 gene locus in South African coloureds: unique allele distributions, novel alleles and gene arrangements. Eur J Clin Pharmacol 2008;64:465-75
  • Chou WH, Yan FX, Robbins-Weilert DK, et al. Comparison of two CYP2D6 genotyping methods and assessment of genotype-phenotype relationships. Clin Chem 2003;49:542-51
  • Zackrisson AL, Lindblom B. Identification of CYP2D6 alleles by single nucleotide polymorphism analysis using pyrosequencing. Eur J Clin Pharmacol 2003;59:521-6
  • Yamada H, Dahl ML, Lannfelt L, et al. CYP2D6 and CYP2C19 genotypes in an elderly Swedish population. Eur J Clin Pharmacol 1998;54:479-81
  • Halling J, Petersen MS, Damkier P, et al. Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. Eur J Clin Pharmacol 2005;61:491-7
  • Griese EU, Zanger UM, Brudermanns U, et al. Assessment of the predictive power of genotypes for the in-vivo catalytic function of CYP2D6 in a German population. Pharmacogenetics 1998;8:15-26
  • Bock KW, Schrenk D, Forster A, et al. The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes. Pharmacogenetics 1994;4:209-18
  • Stamer UM, Bayerer B, Wolf S, et al. Rapid and reliable method for cytochrome P450 2D6 genotyping. Clin Chem 2002;48:1412-17
  • Beer B, Erb R, Pitterl F, et al. CYP2D6 genotyping by liquid chromatography-electrospray ionization mass spectrometry. Anal Bioanal Chem 2011;400:2361-70
  • Tamminga WJ, Wemer J, Oosterhuis B, et al. The prevalence of CYP2D6 and CYP2C19 genotypes in a population of healthy Dutch volunteers. Eur J Clin Pharmacol 2001;57:717-22
  • Rideg O, Haber A, Botz L, et al. Pilot study for the characterization of pharmacogenetically relevant CYP2D6, CYP2C19 and ABCB1 gene polymorphisms in the Hungarian population. Cell Biochem Funct 2011;29:562-8
  • Rebsamen MC, Desmeules J, Daali Y, et al. The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Pharmacogenomics J 2009;9:34-41
  • Crescenti A, Mas S, Gasso P, et al. Simultaneous genotyping of CYP2D6*3, *4, *5 and *6 polymorphisms in a Spanish population through multiplex long polymerase chain reaction and minisequencing multiplex single base extension analysis. Clin Exp Pharmacol Physiol 2007;34:992-7
  • Menoyo A, del Rio E, Baiget M. Characterization of variant alleles of cytochrome CYP2D6 in a Spanish population. Cell Biochem Funct 2006;24:381-5
  • Correia C, Santos P, Coutinho AM, Vicente AM. Characterization of pharmacogenetically relevant CYP2D6 and ABCB1 gene polymorphisms in a Portuguese population sample. Cell Biochem Funct 2009;27:251-5
  • Albuquerque J, Ribeiro C, Naranjo MEG, et al. Characterization of CYP2D6 genotypes and metabolic profiles in the Portuguese population: pharmacogenetic implications. Personalized Medicine 2013;10:709-18
  • Scordo MG, Caputi AP, D’Arrigo C, et al. Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res 2004;50:195-200
  • Arvanitidis K, Ragia G, Iordanidou M, et al. Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population. Fundam Clin Pharmacol 2007;21:419-26
  • Riccardi LN, Lanzellotto R, Luiselli D, et al. CYP2D6 genotyping in natives and immigrants from the Emilia-Romagna region (Italy). Genet Test Mol Biomarkers 2011;15:801-6
  • Gawronska-Szklarz B, Wojcicki M, Kuprianowicz A, et al. CYP2D6 and GSTM1 genotypes in a Polish population. Eur J Clin Pharmacol 1999;55:389-92
  • Niewinski P, Orzechowska-Juzwenko K, Hurkacz M, et al. CYP2D6 extensive, intermediate, and poor phenotypes and genotypes in a Polish population. Eur J Clin Pharmacol 2002;58:533-5
  • Bozina N, Granic P, Lalic Z, et al. Genetic polymorphisms of cytochromes P450: CYP2C9, CYP2C19, and CYP2D6 in Croatian population. Croat Med J 2003;44:425-8
  • Buzkova H, Pechandova K, Slanar O, Perlik F. Frequency of single nucleotide polymorphisms of CYP2D6 in the Czech population. Cell Biochem Funct 2008;26:76-81
  • Marandi T, Dahl ML, Kiivet RA, et al. Debrisoquin and S-mephenytoin hydroxylation phenotypes and CYP2D6 genotypes in an Estonian population. Pharmacol Toxicol 1996;78:303-7
  • Gaikovitch EA, Cascorbi I, Mrozikiewicz PM, et al. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol 2003;59:303-12
  • Marandi T, Dahl ML, Rago L, et al. Debrisoquine and S-mephenytoin hydroxylation polymorphisms in a Russian population living in Estonia. Eur J Clin Pharmacol 1997;53:257-60
  • Attitallah S, Berard M, Belkahia C, et al. Similarities and/or dissimilarities of CYP2D6 polymorphism in three Tunisian ethnic groups: arabs, Berbers, Numides. Therapie 2000;55:355-60
  • Mbanefo C, Bababunmi EA, Mahgoub A, et al. A study of the debrisoquine hydroxylation polymorphism in a Nigerian population. Xenobiotica 1980;10:811-18
  • Iyun AO, Lennard MS, Tucker GT, Woods HF. Metoprolol and debrisoquin metabolism in Nigerians: lack of evidence for polymorphic oxidation. Clin Pharmacol Ther 1986;40:387-94
  • Sommers DK, Moncrieff J, Avenant JC. Absence of polymorphism of sparteine oxidation in the South African Venda. Hum Exp Toxicol 1991;10:175-8
  • Sommers DK, Moncrieff J, Avenant J. Non-correlation between debrisoquine and metoprolol polymorphisms in the Venda. Hum Toxicol 1989;8:365-8
  • Sommers DK, Moncrieff J, Avenant J. Metoprolol alpha-hydroxylation polymorphism in the San Bushmen of Southern Africa. Hum Toxicol 1989;8:39-43
  • Sommers DK, Moncrieff J, Avenant J. Polymorphism of the 4-hydroxylation of debrisoquine in the San Bushmen of Southern Africa. Hum Toxicol 1988;7:273-6
  • Woolhouse NM, Andoh B, Mahgoub A, et al. Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther 1979;26:584-91
  • Woolhouse NM, Eichelbaum M, Oates NS, et al. Dissociation of co-regulatory control of debrisoquin/phenformin and sparteine oxidation in Ghanaians. Clin Pharmacol Ther 1985;37:512-21
  • Nsabiyumva F, Furet Y, Autret E, et al. Oxidative polymorphism of dextromethorphan in a Burundi population. Eur J Clin Pharmacol 1991;41:75-7
  • Gaedigk A, Ndjountche L, Divakaran K, et al. Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Clin Pharmacol Ther 2007;81:242-51
  • He N, Daniel HI, Hajiloo L, Shockley D. Dextromethorphan O-demethylation polymorphism in an African-American population. Eur J Clin Pharmacol 1999;55:457-9
  • Marinac JS, Foxworth JW, Willsie SK. Dextromethorphan polymorphic hepatic oxidation (CYP2D6) in healthy black American adult subjects. Ther Drug Monit 1995;17:120-4
  • Relling MV, Cherrie J, Schell MJ, et al. Lower prevalence of the debrisoquin oxidative poor metabolizer phenotype in American black versus white subjects. Clin Pharmacol Ther 1991;50:308-13
  • Al-Dosari MS, Al-Jenoobi FI, Alkharfy KM, et al. High prevalence of CYP2D6*41 (G2988A) allele in Saudi Arabians. Environ Toxicol Pharmacol 2013;36:1063-7
  • McLellan RA, Oscarson M, Seidegard J, et al. Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics 1997;7:187-91
  • Qumsieh RY, Ali BR, Abdulrazzaq YM, et al. Identification of new alleles and the determination of alleles and genotypes frequencies at the CYP2D6 gene in Emiratis. PLoS One 2011;6:e28943
  • Afshar M, Rouini M, Ala S. Dextromethorphan metabolic phenotyping in an Iranian population. Eur J Clin Pharmacol 2005;60:849-54
  • Evans DA, Krahn P, Narayanan N. The mephenytoin (cytochrome P450 2C 19) and dextromethorphan (cytochrome P450 2D6) polymorphisms in Saudi Arabians and Filipinos. Pharmacogenetics 1995;5:64-71
  • al-Hadidi HF, Irshaid YM, Rawashdeh NM. Metoprolol alpha-hydroxylation is a poor probe for debrizoquine oxidation (CYP2D6) polymorphism in Jordanians. Eur J Clin Pharmacol 1994;47:311-14
  • Irshaid YM, al-Hadidi HF, Rawashdeh NM. Dextromethorphan O-demethylation polymorphism in Jordanians. Eur J Clin Pharmacol 1993;45:271-3
  • Basci NE, Bozkurt A, Isimer A, Kayaalp SO. Correlation between the metabolic ratios of debrisoquine and metoprolol in Turkish subjects. Pharmacol Toxicol 1994;75:62-4
  • Islam SI, Idle JR, Smith RL. The polymorphic 4-hydroxylation of debrisoquine in a Saudi Arab population. Xenobiotica 1980;10:819-25
  • Weerasuriya K, Jayakody RL, Smith CA, et al. Debrisoquine and mephenytoin oxidation in Sinhalese: a population study. Br J Clin Pharmacol 1994;38:466-70
  • Mamidi RN, Satyavageeswaran S, Vakkalanka SV, et al. Polymorphism of dextromethorphan oxidation in South Indian subjects. Clin Pharmacol Ther 1999;66:193-200
  • Lamba V, Lamba JK, Dilawari JB, Kohli KK. Genetic polymorphism of CYP2D6 in North Indian subjects. Eur J Clin Pharmacol 1998;54:787-91
  • Abraham BK, Adithan C, Shashindran CH, et al. Genetic polymorphism of CYP2D6 in a Keralite (South India) population. Br J Clin Pharmacol 2000;49:285-6
  • Abraham BK, Adithan C, Kiran PU, et al. Genetic polymorphism of CYP2D6 in Karnataka and Andhra Pradesh population in India. Acta Pharmacol Sin 2000;21:494-8
  • Straka RJ, Hansen SR, Walker PF. Comparison of the prevalence of the poor metabolizer phenotype for CYP2D6 between 203 Hmong subjects and 280 white subjects residing in Minnesota. Clin Pharmacol Ther 1995;58:29-34
  • Ismail R, Hussein A, Teh LK, Nizam Isa M. CYP2D6 phenotypes among Malays in Malaysia. J Clin Pharm Ther 2000;25:379-83
  • Wanwimolruk S, Patamasucon P, Lee EJ. Evidence for the polymorphic oxidation of debrisoquine in the Thai population. Br J Clin Pharmacol 1990;29:244-7
  • Johansson I, Yue QY, Dahl ML, et al. Genetic analysis of the interethnic difference between Chinese and Caucasians in the polymorphic metabolism of debrisoquine and codeine. Eur J Clin Pharmacol 1991;40:553-6
  • Cai WM, Chen B, Liu YX, Chu X. Dextromethorphan metabolic phenotyping in a Chinese population. Zhongguo Yao Li Xue Bao 1997;18:441-4
  • Kubota T, Yamaura Y, Ohkawa N, et al. 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 2000;50:31-4
  • Lane HY, Deng HC, Huang SM, et al. Low frequency of dextromethorphan O-demethylation deficiency in a Chinese population. Clin Pharmacol Ther 1996;60:696-8
  • Wang SL, Huang JD, Lai MD, et al. Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 1993;53:410-18
  • Lee EJ, Jeyaseelan K. Frequency of human CYP2D6 mutant alleles in a normal Chinese population. Br J Clin Pharmacol 1994;37:605-7
  • Roh HK, Dahl ML, Johansson I, et al. Debrisoquine and S-mephenytoin hydroxylation phenotypes and genotypes in a Korean population. Pharmacogenetics 1996;6:441-7
  • Chida M, Yokoi T, Nemoto N, et al. A new variant CYP2D6 allele (CYP2D6*21) with a single base insertion in exon 5 in a Japanese population associated with a poor metabolizer phenotype. Pharmacogenetics 1999;9:287-93
  • Lou YC, Ying L, Bertilsson L, Sjoqvist F. Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet 1987;2:852-3
  • Nakamura K, Goto F, Ray WA, et al. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 1985;38:402-8
  • Ishizaki T, Eichelbaum M, Horai Y, et al. Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol 1987;23:482-5
  • Cai WM, Chen B, Zhang WX. Frequency of CYP2D6*10 and *14 alleles and their influence on the metabolic activity of CYP2D6 in a healthy Chinese population. Clin Pharmacol Ther 2007;81:95-8
  • Wanwimolruk S, Bhawan S, Coville PF, Chalcroft SC. Genetic polymorphism of debrisoquine (CYP2D6) and proguanil (CYP2C19) in South Pacific Polynesian populations. Eur J Clin Pharmacol 1998;54:431-5
  • Brosen K. Sparteine oxidation polymorphism in Greenlanders living in Denmark. Br J Clin Pharmacol 1986;22:415-19
  • Arvela P, Kirjarinta M, Kirjarinta M, et al. Polymorphism of debrisoquine hydroxylation among Finns and Lapps. Br J Clin Pharmacol 1988;26:601-3
  • Arias TD, Jorge LF, Inaba T. No evidence for the presence of poor metabolizers of sparteine in an Amerindian group: the Cunas of Panama. Br J Clin Pharmacol 1986;21:547-8
  • Estevez F, Giusti M, Parrillo S, Oxandabarat J. Dextromethorphan O-demethylation polymorphism in the Uruguayan population. Eur J Clin Pharmacol 1997;52:417-18
  • Peart GF, Boutagy J, Shenfield GM. Debrisoquine oxidation in an Australian population. Br J Clin Pharmacol 1986;21:465-71
  • Turgeon J, Evans WE, Relling MV, et al. Phenotypic debrisoquine 4-hydroxylase activity among extensive metabolizers is unrelated to genotype as determined by the Xba-I restriction fragment length polymorphism. Br J Clin Pharmacol 1991;32:283-8
  • Madsen H, Nielsen KK, Brosen K. Imipramine metabolism in relation to the sparteine and mephenytoin oxidation polymorphisms–a population study. Br J Clin Pharmacol 1995;39:433-9
  • Pedersen RS, Damkier P, Brosen K. Tramadol as a new probe for cytochrome P450 2D6 phenotyping: a population study. Clin Pharmacol Ther 2005;77:458-67
  • Steiner E, Bertilsson L, Sawe J, et al. Polymorphic debrisoquin hydroxylation in 757 Swedish subjects. Clin Pharmacol Ther 1988;44:431-5
  • Drohse A, Bathum L, Brosen K, Gram LF. Mephenytoin and sparteine oxidation: genetic polymorphisms in Denmark. Br J Clin Pharmacol 1989;27:620-5
  • Sanz EJ, Villen T, Alm C, Bertilsson L. S-mephenytoin hydroxylation phenotypes in a Swedish population determined after coadministration with debrisoquin. Clin Pharmacol Ther 1989;45:495-9
  • Brosen K, Otton SV, Gram LF. Sparteine oxidation polymorphism in Denmark. Acta Pharmacol Toxicol (Copenh) 1985;57:357-60
  • Tamminga WJ, Wemer J, Oosterhuis B, et al. CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol 1999;55:177-84
  • Paar WD, Schuhler H, Fimmers R, Dengler HJ. Sparteine oxidation polymorphism: phenotyping by measurement of sparteine and its dehydrometabolites in plasma. Eur J Clin Pharmacol 1989;36:555-60
  • Leclercq V, Desager JP, van Nieuwenhuyze Y, Harvengt C. Prevalence of drug hydroxylator phenotypes in Belgium. Eur J Clin Pharmacol 1987;33:439-40
  • Szorady I, Santa A. Drug hydroxylator phenotype in Hungary. Eur J Clin Pharmacol 1987;32:325
  • Evans DA, Mahgoub A, Sloan TP, et al. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet 1980;17:102-5
  • Schmid B, Bircher J, Preisig R, Kupfer A. Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther 1985;38:618-24
  • Dick B, Kupfer A, Molnar J, et al. Drug hydroxylation disorders (debrisoquin type) in a random sample of the Swiss population. Schweiz Med Wochenschr 1982;112:1061-7
  • Zimmermann T, Schlenk R, Pfaff G, et al. Prediction of phenotype for dextromethorphan O-demethylation by using polymerase chain reaction in healthy volunteers. Arzneimittelforschung 1995;45:41-3
  • Funck-Brentano C, Boelle PY, Verstuyft C, et al. Measurement of CYP2D6 and CYP3A4 activity in vivo with dextromethorphan: sources of variability and predictors of adverse effects in 419 healthy subjects. Eur J Clin Pharmacol 2005;61:821-9
  • Kimiskidis VK, Niopas I, Firinidis PD, et al. Frequency distribution of dextromethorphan O-demethylation in a Greek population. Int J Clin Pharmacol Ther 2005;43:150-3
  • Llerena A, Edman G, Cobaleda J, et al. Relationship between personality and debrisoquine hydroxylation capacity. Suggestion of an endogenous neuroactive substrate or product of the cytochrome P4502D6. Acta Psychiatr Scand 1993;87:23-8
  • Spina E, Campo GM, Avenoso A, et al. CYP2D6-related oxidation polymorphism in Italy. Pharmacol Res 1994;29:281-9
  • Jacqz E, Dulac H, Mathieu H. Phenotyping polymorphic drug metabolism in the French Caucasian population. Eur J Clin Pharmacol 1988;35:167-71
  • Larrey D, Amouyal G, Tinel M, et al. Polymorphism of dextromethorphan oxidation in a French population. Br J Clin Pharmacol 1987;24:676-9
  • Freche JP, Dragacci S, Petit AM, et al. Development of an ELISA to study the polymorphism of dextromethorphan oxidation in a French population. Eur J Clin Pharmacol 1990;39:481-5
  • Henthorn TK, Benitez J, Avram MJ, et al. Assessment of the debrisoquin and dextromethorphan phenotyping tests by Gaussian mixture distributions analysis. Clin Pharmacol Ther 1989;45:328-33
  • Benitez J, LLerena A, Cobaleda J. Debrisoquin oxidation polymorphism in a Spanish population. Clin Pharmacol Ther 1988;44:74-7
  • Kunicki PK, Sitkiewicz D, Pawlik A, et al. Debrisoquine hydroxylation in a Polish population. Eur J Clin Pharmacol 1995;47:503-5
  • Skretkowicz J, Wojtczak A, Rychlik-Sych M. Polymorphism of dextromethorphan oxidation in Polish population. Acta Pol Pharm 2008;65:611-15

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.