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Research Article

Genetic Polymorphisms in Human Drug-Metabolizing Enzymes: Potential Uses of Reverse Genetics to Identify Genes of Toxicological Relevance

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Pages 199-222 | Published online: 25 Sep 2008

References

  • Kalow W. Pharmacogenetics: its biological roots and the medical challenge. Clin. Pharmacol. Ther. 1993; 54: 235
  • Kalow W. Life of a pharmacologist or the rich life of a poor metabolizer (invited autobiographical account). Pharmacol. Toxicol 1995; 76: 221
  • Motulsky A. G. Pharmacogenetics and ecogenetics in 1991. Pharmacogenetics 1991; 1: 2
  • Caporaso N. E., Goldstein A. Cancer genes: single and susceptibility: exposing the difference. Pharmacogenetics 1995; 5: 59
  • Nebert D. W., Gonzalez F. J. P450 genes. Structure, evolution and regulation. Annu. Rev. Biochem. 1987; 56: 945
  • Nebert D. W., McKinnon R. A. Cytochrome P450: evolution and functional diversity. Prog. Liver Dis. 1994; 12: 63
  • Nelson D. R., Kamataki T., Waxman D. J., Guengerlch F. P., Estabrook R. W., Feyereisen R., Gonzalez F. J., Coon M. J., Gunsalus I. C., Gotoh O., et al. The P450 superfamily: update on new sequences, gane mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 1993; 12: 1
  • Nebert D. W., Nelson D. R., Coon M. J., Estabrook R. W., Feyereisen R., Fujii-Kuriyama Y., Gonzalez F. J., Guengerich F. P., Gunsalus I. C., Johnson E. F., et al. The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 1991; 10: 1
  • Lawton M. P., Cashman J. R., Cresteil T., Dolphin C. T., Elfarra A. A., Hines R. N., Hodgson E., Kimura T., Ozols J., Phillips I. R., et al. Mammalian flavin-containing monooxygenase gene families based on amino acid sequence identities. Arch. Biochem. Biophys. 1994; 308: 254
  • Burchell B., Nebert D. W., Nelson D. R., Bock K. W., Iyanagi T., Jansen P. L. M., Lancet D., Mulder G. J., Chowdhury J. R., Siest G., et al. The UDP-glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence. DNA Cell Biol 1991; 10: 487
  • Nebert D. W. Identification of genetic differences in drug metabolism: prediction of individual risk of toxicity or cancer. Hepatology 1991; 14: 398
  • Nebert D. W. Role of genetics and drug metabolism in human cancer risk. Mutat. Res. 1991; 247: 267
  • Nebert D. W. The Ahlocus: genetic differences in toxicity, cancer, mutation, and birth defects. Crit. Rev. Toxicol. 1989; 20: 153
  • Nebert D. W., Petersen D. D., Puga A. Human AH locus polymorphism and cancer: inducibility ofCYP1A1 and other genes by combustion products and dioxin. Pharmacogenetics 1991; 1: 68
  • Gonzalez F. J. The molecular biology of cytochrome P450s. Pharmacol. Rev. 1988; 40: 243
  • Greenlee W. F., Neal R. A. The Ahreceptor: a biochemical and biological perspective. The Receptors, P. M. Conn. Academic-Press, New York 1985; Vol. 2: 89
  • Burbach K. ML, Poland A., Bradfield C. A. Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. U.S.A. 1992; 89: 8185
  • Ema M., Sogawa K., Watanabe N., Chujoh Y., Matsushita N., Gotoh O., Funae Y., Fujii-Kuriyama Y. cDNA cloning and structure of mouse putative Ah receptor. Biochem. Biophys. Res. Commitn. 1992; 184: 246
  • Hankinson O. Research on the aryl hydrocarbon (dioxin) receptor is primed to take off. Arch. Biochem. Biophys. 1993; 300: 1
  • Swanson H. I., Bradfield C. A. The AH-recep-tor: genetics, structure and function. Pharmacogenetics 1993; 3: 213
  • Landers J. P., Bunce N. J. The Ahreceptor and the mechanism of dioxin toxicity. Biochem. J. 1991; 276: 273
  • Nebert D. W., Puga A., Vasiliou V. Role of the Ah receptor and dioxin inducible[Ah] gene battery in toxicity, cancer, and signal transduction.Ann. /V. Y. Acad. Sci. 1993; 685: 624
  • Whitlock J. P., Jr. Genetic and molecular aspects of 2.3.7,K-tetrachlorodibenzo-p-dioxin action. Anna. Rev. Pharmacol. Toxicol 1991; 30: 251
  • Poland A., Glover E., Robinson J. R., Nebert D. W. Genetic expression of aryl hydrocarbon hydroxylase activity. Induction of monooxygenase activities and cytochrome P,-450 formation by 2.3.7.8-tetrachlorodibenzo-/j-dioxin in mice genetically “non-responsive” to other aromatic hydrocarbons. J. Biol. Chem. 1974; 249: 5599
  • Poland A., Palen D., Glover E. Analysis of the four alleles of the murine aryl hydrocarbon receptor. Mol. Pharmacol. 1994; 46: 915
  • Ema M., Ohe N., Suzuki M., Mimura J., Sogawa K., Ikawa S., Fujii-Kuriyama Y. Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors. J. Biol. Chem. 1994; 269: 27337
  • Chang C. Y., Smith D. R., Prasad V. S., Sidman C. L., Nebert D. W., Puga A. Ten nucleotide differences, five of which cause amino acid changes. are associated with the Ah receptor locus polymorphism of C57BL/6 and DBA/2 mice. Pharmacogenetics 1993; 3: 312
  • Roberts E. A., Golas C. L., Okey A. B. Ahreceptor mediated induction of aryl hydrocarbon hydroxylase: detection in human lung by binding of 2,3,7.8-[-,H]tetrachlorodibenzo-p-dioxin. Cancer Res. 1986; 46: 3739
  • Vanden Heuvel J. P., Clark G. C., Thompson C. L., McCoy Z., Miller C. R., Lucier G. W., Bell D. A. CYP1 Al mRNA levels as a human exposure biomarker: use of quantitative polymerase chain reaction to measure CYP1A1 expression in human peripheral blood lymphocytes. Carcinogenesis 1993; 14: 2003
  • Kellerman G., Shaw C. R., Luyten-Kellerman M. Aryl hydrocarbon hydroxylase inducibility and bronchogenic carcinoma. N. Engl. J. Med. 1973; 289: 934
  • Fingerhut M. A., Halperin W. E., Marlow D. A., Piacitelli L. A., Honchar P. A., Sweeney M. H., Greife A. L., Dill P. A., Steenland K., Suruda A. J. Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N. Engl. J. Med. 1991; 324: 212
  • Manz A., Berger J., Dwyer J. H., Flesch-Janys D., Nagel S., Waltsgott H. Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet 1991; 338: 959
  • Bertazzi P. A. Long-term effects of chemical disasters. Lessons and results from Seveso. Sci. Total Environ. 1991; 106: 5
  • Kouri R. E., McKinney C. E., Slomiany D. J., Snodgrass D. R., Wray N. P., McLemore T. L. Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res. 1982; 42: 5030
  • Coombs M. L., Mason W. A., Muijsson I. E., Cantrell E. T., Anderson D. E., Busbee D. L. Aryl hydrocarbon hydroxylase and testosterone 16oc-hydroxylase in cultured human lymphocytes. Biochem. Genet. 1976; 14: 671
  • Guirgis H. A., Lynch H. T., Mate T., Harris R. E., Wells I., Caha L., Anderson J., Maloney K., Rankin L. Aryl hydrocarbon hydroxylase activity in lymphocytes from lung cancer patients and normal controls. Oncology 1976; 33: 105
  • Emery A. E. H., Danford N., Anand R., Duncam W., Paton L. Aryl hydrocarbon hydroxylase inducibility in patients with cancer. Lancet 1978; 1: 470
  • Korsgaard R., Trell E. Aryl hydrocarbon hydroxylase and bronchogenic carcinomas associated with smoking. Lancet 1978; 1: 1103
  • Arnott M. S., Yamauchi T., Johnston D. A. Aryl hydrocarbon hydroxylase in normal and cancer populations. Carcinogens: Identification and Mechanisms of Action, A. C. Griffin, C. R Shaw. Raven Press, New York 1979; 145
  • Gahmberg C. G., Sekki A., Kosunen T. U., Holsti L. R., Makela O. Induction of aryl hydrocarbon hydroxylase activity and pulmonary carcinoma. Int. J. Cancer 1979; 23: 302
  • McLemore T. L., Martin R. R., Springer R. R., Wray N., Cantrell E. T., Busbee D. L. Aryl hydrocarbon hydroxylase acticity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients. Biochem. Genet. 1979; 17: 795
  • Trell E., Körsgaard R., Hood B., Kitzing P., Norden G., Simonsson B. G. Aryl hydrocarbon hydroxylase inducibility and laryngeal carcinomas. Lancet 1976; 2: 140
  • Trell E., Körsgaard R. Smoking and oral carcinoma. Lancet 1978; 1: 671
  • Trell E., Körsgaard R., Kitzing P., Lundgren K., Mattiasson I. Aryl hydrocarbon inducibility and carcinoma of oral cavity. Lancet 1978; 1: 109
  • Shields P. G., Sugimura H., Caporaso N. E., Petruzzelli S. F., Bowman E. D., Trump B. F., Weston A., Harris C. Polycyclic aromatic hydrocarbon-DNA adducts and theCYP1AI RFLP. Environ. Health Perspect 1992; 98: 191
  • Trell E., Oldbring J., Körsgaard R., Mattiasson I. Aryl hydrocarbon hydroxylase inducibility in carcinoma of renal pelvis and ureter. Lancet 1977; 2: 612
  • Trell E., Oldbring J., Körsgaard R., Hellsten S., Mattiasson I., Telhammar E. Aryl hydrocarbon hydroxylase inducibility and carcinoma of the urinary bladder. IRCS J. Med. Set 1978; 6: 138
  • Gurtoo H. L., Minowada J., Paigen B., Parker N. B., Hayner N. T. Factors influencing the measurement and the reproducibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. J. Nat. Cancer Inst 1977; 59: 787
  • Jett J. R., Moses H. L., Branum E. L., Taylor W. F., Fontana R. S. Benzo[a]pyrene metabolism and blast formation in peripheral blood mononuclear cells from smoking and non-smoking populations and lung cancer patients. Cancer 1978; 41: 192
  • Lieberman J. Aryl hydrocarbon hydroxylase in bronchogenic carcinoma. N. Engl. J. Med. 1978; 298: 686
  • Paigen B., Gurtoo H. L., Minowada J., Houten L., Vincent R., Paigen K., Parker N. B., Ward E., Hayner N. T. Questionable relation of aryl hydrocarbon hydroxylase to lung cancer risk. N. Engl. J. Med. 1977; 297: 346
  • Ward E., Paigen B., Steenland K., Vincent R., Minowada J., Gurtoo H. L., Sartori P., Havens M. B. Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer. Int. J. Cancer 1979; 23: 312
  • Landi M. T., Bertazzi P. A., Shields P. G., Clark G., Lucier G. W., Garte S. J., Cosma G., Caporaso N. E. Association between CYP1AI genotype, mRNA expression and enzymatic activity in humans. Pharmacogenetics 1994; 4: 242
  • Dolwick K. M., Schmidt J. V., Carver L. A., Swanson H. I., Bradtield C. A. Cloning and expression of a human Ah receptor cDNA. Mol. Pharmacol. 1993; 44: 911
  • Takahashi Y., Itoh S., Shimojima T., Kamataki T. Characterization of Ah receptor promoter in human liver cell line, HepG2. Pharmacogenetics 1994; 4: 219
  • Fujii-Kuriyama Y., Ema M., Matsushita N., Sogawa K. Polymorphic forms of the Ah receptor and induction of theCYP1A1 gene. Pharmacogenetics 1995; 5: S149
  • Fernandez-Salguero P., Pineau T., Hilbert D. M., McPhail T., Lee S. S. T., Kimura S., Nebert D. W., Rudikoff S., Ward J. M., Gonzalez F. J. Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 1995; 268: 722
  • Kimura S., Gonzalez F. J., Nebert D. W. The murine Ahlocus. Comparison of the complete cytochrome P1-450 and P2-450 cDNA nucleotide and amino acid sequences. J. Biol. Chem. 1984; 259: 10705
  • Bale A. E., Nebert D. W., McBride O. W. Subchromosomal localization of the dioxin-inducible P,450 locus(CYP1) and description of two RFLP's detected with a 3′P1450 cDNA probe. Cytogen. Cell Genet. 1987; 46: 574
  • Kawajiri K., Nakachi K., Imai K., Yoshii A., Shinoda N., Watanabe J. Identification of genetically high risk individuals to lung cancer by polymorphisms of the cytochrome P450IA1 gene. FEBS Lett. 1990; 263: 131
  • Hayashi S. I., Watanabe J., Nakachi K., Kawajiri K. Genetic linkage of lung cancer-associates Msp I polymorphisms with amino acid replacement in the heme-binding region of the human cytochrome P450IA1 gene. J. Biochem. (Tokyo) 1991; 110: 407
  • Hayashi S. I., Watanabe J., Nakachi K., Kawajiri K. PCR detection of an A/G polymorphism within exon 7 of the CYP1A1 gene. Nucleic Acids Res. 1991; 19: 4797
  • Hayashi S., Watanabe J., Kawajiri K. High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes. Jpn. J. Cancer Res. 1992; 83: 866
  • Nakachi K., Imai K., Hayashi S., Kawajiri K. Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res. 1993; 53: 2994
  • Tefre T., Ryberg D., Haugen A., Nebert D. W., Skaug V., Brogger A., Borresen A. L. Human CYP1A1 (cytochrome P1450) gene: lack of association between theMsp I restriction fragment length polymorphism and incidence of lung cancer in a Norwegian population. Pharmacogenetics 1991; 1: 20
  • Shields P. G., Bowman E. D., Harrington A. M., Doan V. T., Weston A. Polycyclic aromatic hydrocarbon-DNA adducts in human lung and cancer susceptibility genes. Cancer Res. 1993; 53: 3486
  • Hirvonen A., Husgafvel-Pursiainen K., Karjalainen A., Anttila S., Vainio H. Point-mutational Mspl and Ile-Val polymorphisms closely linked in the CYP1 Al gene: lack of association with susceptibility to lung cancer in a Finnish study population. Cancer Epidemiol. Biomark. Prev. 1992; 1: 485
  • Hirvonen A., Husgafvel-Pursiainen K., Anttila S., Karjalainen A., Sorsa M., Vainio H. Metabolic cytochrome P450 genotypes and assessment of individual susceptibility to lung cancer. Pharmacogenetics 1992; 2: 259
  • Wedlund P. J., Kimura S., Gonzalez F. J., Nebert D. W. 1462V mutation in the human CYP1A1 gene: lack of correlation with either the Msp I 1.9 kb (M2) allele or CYP1 Al inducibility in a three-generation family of east Mediterranean descent. Pharmacogenetics, 4: 21, 994
  • Crofts F., Cosma G. N., Currie D., Taioli E., Toniolo P., Garte S. J. A novel CYP1 Al gene polymorphism in African-Americans. Carcinogenesis 1993; 14: 1729
  • Taioli E., Crofts F., Trachman J., Demopoulos R., Toniolo P., Garte S. J. A specific African-AmericanCYP1A1 polymorphism is associated with adenocarcinoma of the lung. Cancer Res. 1995; 55: 472
  • Kelsey K. T., Wiencke J. K., Spitz M. R. A race-specific genetic polymorphism in theCYPIA1 gene is not associated with lung cancer in African-Americans. Carcinogenesis 1994; 15: 1121
  • London S. J., Daly A. K., Fairbrother K., Holmes C., Carpenter C. L., Navidi W. C., Idle J. R. Lung cancer risk in African-Americans in relation to a races-pecificCYPIAI polymorphism. Cancer Res. 1995; 55: 6035
  • Taioli E., Trachman J., Chen X., Toniolo P., Garte S. J. ACYPIAI restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res. 1995; 55: 3757
  • Mahgoub A., Idle J. R., Dring L. G., Lancaster R., Smith R. L. Polymorphic hydroxylation of debrisoquine in man. Lancet 1977; 2: 584
  • Gonzalez F. J., Meyer U. A. Molecular genetics of the debrisoquine-sparteine polymorphism. Clin. Pharmacol. Ther. 1991; 50: 233
  • Johansson I., Oscarson M., Yue Q. Y., Bertilsson L., Sjoqvist F., Ingelman-Sundberg M. Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol. Pharmacol 1994; 46: 452
  • Bertilsson L., Lou Y. Q., Dy Y. L., Liu Y., Kuang T. Y., Liao X. ML, Wang K. Y., Reviriego J., Iselius L., Sjöqvist F. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquine and S-mephenytoin. Clin. Pharmacol. Ther. 1992; 51: 388
  • Mannervik B., Awasthi Y. C., Board P. G., Hayes J. D., Di Hio C., Ketterer B., Listowsky I., Morgenstern R., Muramatsu M., Pearson W. R., et al. Nomeclature for human glutathione transferases. Biochem. J. 1992; 282: 305
  • Buchert E. T., Woosley R. L. Clinical implications of variable antiarrhythmic drug metabolism. Pharmacogenetics 1992; 2: 2
  • Nebert D. W. Polymorphism of human CYP2D genes involved in drug metabolism: possible relationship to individual cancer risk. Cancer Cells 1991; 3: 93
  • Gonzalez F. J., Idle J. R. Pharmacogenetic phenotyping and genotyping: present status and future potential. Clin. Pharmacokinet. 1994; 26: 59
  • Caporaso N., DeBaun M. R., Rothman N. Lung cancer andCYP2D6 (the debrisoquine polymorphism): sources of heterogeneity in the proposed association. Pharmacogenetics 1995; 5: S129
  • Steen V., Andreassen O. A., Daly A. K., Tefre T., Borresen A. L., Idle J. R., Gulbrandsen A. K. Detection of the poor metabolizer-associatedCYP2D6(D) gene deletion allele by long-PCR methodology. Pharmacogenetics 1995; 5: 215
  • Meyer U. A. Pharmacogenetics: the slow, the rapid and the ultrarapid. Proc. Natl. Acad. Sci. U.S.A. 1994; 91: 1983
  • Barbeau A. E., Cloutier T., Roy M., Plasse L., Paris S., Poirier J. Ecogenetics of Parkinson's disease: 4-hydroxylation of debrisoquine. Lancet 1985; 2: 1213
  • Poirier J., Roy M., Campanella G., Cloutier T., Paris S. Debrisoquine metabolism in Parkinsonian patients treated with antihistamine drugs. Lancet 1987; 2: 386
  • Steventon G. B., Heathfield M. T. E., Waring R. H., Williams A. C. Xenobiotic metabolism in Parkinson's disease. Neurology 1989; 39: 883
  • Steiger M. J., Lledo P., Quinn N. P., Marsden C. D., Turner P., Jenner P. G. Debrisoquine hydroxylation in Parkinson's disease. Acta Neurol Scand 1992; 86: 159
  • Gudjonsson O., Sanz E., Alvan G., Aquilonius S. M., Reviriego J. Poor hydroxylator pheno-types of debrisoquine are not overrepresented in a group of patients with Parkinson's disease. Br. J. Clin. Pharmacol 1990; 30: 301
  • Kallio J., Martilli R. J., Rinne U. K., Sonninen V., Syvälathi E. Debrisoquine oxidation in Parkinson's disease. Acta Neurol. Scand. 1991; 83: 194
  • Kondo I., Kanazawa I. Debrisoquine hydroxylase and Parkinson's disease. Adv. Neurol. 1993; 60: 338
  • Armstrong M., Daly A. K., Cholerton S., Bateman D. N., Idle J. R. Mutant debrisoquine hydroxy-lation genes in Parkinson's disease. Lancet 1992; 339: 1017
  • Smith C. A. D., Gough A. C., Leigh P. N., Summers B. A., Harding A. E., Maranganore D. M., Sturman S. G., Schapira A. H. V., Williams A. C., Spurr N. K., et al. Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease. Lancet 1992; 339: 1375
  • Tyndale R. F., Sunahara R., Inaba T., Kalow W., Gonzalez F. J., Niznik H. B. Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Mol. Pharmacol 1991; 40: 63
  • Sindrup S. H., Poulsen L., Brosen K., Arendt-Nielsen L., Gram L. F. Are poor metabolisers of sparteine/debrisoquine less pain tolerant than extensive metabolisers?. Pain 1993; 53: 335
  • Sindrup S. H., Brosen K. The pharmacogenetics of codeine hypoalgesia. Pharmacogenetics 1995; 5: 335
  • Ayesh R., Idle J. R., Ritchie J. C., Crothers M. J., Hetzel M. R. Metabolic oxidation pheno-types are markers for susceptibility to lung cancer. Nature, (London) 1984; 312: 169
  • Roots I., Drakoulis N., Bröckmoller J. Polymorphic enzymes and cancer risk: concepts, methodology and data review. Pharmacogenetics of Drug Metabolism, W. Kalow. Pergamon Press, New York 1992; 815
  • Ingelman-Sundberg M., Johansson I., Persson I., Yue Q. Y., Dahl M. L., Bertilsson L., Sjöqvist F. Genetic polymorphism of cytochromes P450: in-terethnic differences and relationship to incidence of lung cancer. Pharmacogenetics 1992; 2: 264
  • Caporaso N. E., Tucker M. A., Hoover R. N., Hayes R. B., Pickle L. W., Issaq H. J., Muschik G. M., Green-Gallo L., Buivys D., Aisner S., et al. Lung cancer and the debrisoquine metabolic phe-notype. J. Natl. Cancer Inst. 1990; 82: 1264
  • Cholerton S., Arpanahi A., McCracken N., Boustead C., Taber H., Johnstone E., Leathart J., Daly A. K., Idle J. R. Poor metabolisers of nicotine andCYP2D6 polymorphism. Lancet 1994; 343: 62
  • Koop D. R. Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J. 1992; 6: 724
  • Snawder J. E., Roe A. L., Benson R. W., Casciano D. A., Roberts D. W. Cytochrome P450-depen-dent metabolism of acetaminophen in four human transgenic lymphoblastoid cell lines. Pharmacogenetics 1994; 4: 43
  • Guengerich F. P., Kim D. H., Iwasaki M. Role of human P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol 1991; 4: 168
  • Guengerich F. P. Polymorphism of cytochrome P-450 in humans. Trends Pharmacol. Set 1989; 10: 107
  • Daly A. K., Cholerton S., Armstrong M., Idle J. R. Genotyping for polymorphisms in xenobiotic metabolism as a predictor of disease susceptibility. Environ. Health Perspect. 1994; 102(Suppl. 9)55
  • McBride O. W., Umeno M., Gelboin H. V., Gonzalez F. J. Taq I polymorphism in the human P450IIE1 gene on chromosome 10 (CYP2E), Nucleic Acids Res. 1987; 15: 10071
  • Uematsu F., Kikuchi H., Ohmachi T., Sagami I., Motomiya M., Kamataki T., Komori M., Watanabe M. Two common RFLPs of theCYP2E gene. Nucleic Acids Res. 1991; 19: 2803
  • Hayashi S., Watanabe J., Kawajiri K. Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J. Biochem. 1991; 110: 559
  • Watanabe J., Hayashi S. L, Nakachi K., Imai K., Suda Y., Sekine T., Kawajiri K. Pst I andRsa I RFLP in complete linkage disequilibrium at theCYP2E1 gene, Nucleic Acids Res. 1990; 18: 7194
  • Stephens E. A., Taylor J. A., Kaplan N., Yang C. H., Hsieh L. L., Lucier G. W., Bell D. A. Ethnic variation in theCYP2E1 gene: polymorphism analysis of 695 African-Americans, European-Americans and Taiwanese. Pharmacogenetics 1994; 4: 185
  • Uematsu F., Kikuchi H., Motomiya M., Abe T., Sagami I., Ohmachi T., Wakui A., Kanamaru R., Watanabe M. Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to lung cancer. Jpn. J. Cancer Res. 1991; 82: 254
  • Persson I., Johansson I., Bergling H., Dahl M. L., Seidegard J., Rylander R., Rannug A., Hogberg J., Ingelman-Sundberg M. Genetic polymorphism of cytochrome P4502E1 in a Swedish population: relationship to lung cancer. FEBS Lett. 1993; 319: 207
  • Uematsu F., Ikawa S., Kikuchi H., Sagami I., Kanamaru R., Abe T., Satoh K., Motomiya M., Watanabe M. Restriction fragment length polymorphism of the humanCYP2E1 (cytochrome P450IIE1) gene and susceptibility to lung cancer: possible relevance to low smoking exposure. Pharmacogenetics 1994; 4: 58
  • Tsutsumi M., Lasker J. M., Shimizu M., Rosman A. S., Lieber C. S. The intralobular distribution of ethanol-inducible P450IIE1 in rat and human liver. Hepatology 1989; 10: 437
  • Wrighton S. A., Thomas P. E., Molowa D. T., Haniu M., Shively J. F., Maines S. L., Watkins P. B., Parker G., Mendez-Picon G., Levin W., et al. Characterization of ethanol-inducible human liverN-nitrosodimethylamine demethylase. Biochemistry 1986; 25: 6371
  • Takahashi T., Lasker J. M., Rosman A. S., Lieber C. S. Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase of encoding mRNA. Hepatolagy 1992; 17: 236
  • Peterson F. J., Holloway D. E., Erickson R. R., Duquette P. H., McClain C. J., Holtzman J. L. Ethanol induction of acetaminophen toxicity and metabolism. Life Sci. 1980; 37: 1705
  • Lucas D., Ménez C., Girre C., Berthou F., Bodénez P., Joannet I., Hispard E., Bardou L. G., Ménez J. F. CytochromeP450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic-Caucasian subjects. Pharmacogenetics 1995; 5: 298
  • Ayesh R., Mitchell S. C., Smith R. L. Body malodour syndromes. Lancet 1995; 345: 1308
  • Ayesh R., Mitchell S. C., Zhang A., Smith R. L. The fish odour syndrome: biochemical, familial. and clinical aspects. BMJ 1993; 307: 655, (see comments)
  • Dolphin C., Shephard E. A., Povey S., Palmer C. N., Ziegler D. M., Ayesh R., Smith R. L., Phillips I. R. Cloning, primary sequence, and chromosomal mapping of a human flavin-containing monooxygenase (FMOD.i. Biol. Chem. 1991; 266: 12379
  • Grant D M. Molecular genetics of the N-acetyl-transferases. Pharmacogenetics 1993; 3: 45
  • Lawton M. P., Philpot R. M. Molecular genetics of the flavin-dependent monooxygenases. Pharmacogenetics 1993; 3: 40
  • Hines R. N., Cashman J. R., Philpot R. M., Williams D. E., Ziegler D. M. The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression. Toxicol. Appl. Pharmacol. 1994; 125: 1
  • Seidegard J., DePierre J. Microsomal epoxide hydrolase properties, regulation and function. Biochim. Biophys. Acta 1983; 695: 251
  • Farin F. M., Omiecinski C. J. Regiospecific expression of cytochrome P-450s and microsomal epoxide hydrolase in human brain tissue. J. Toxicol. Environ. Health 1993; 40: 317
  • Farin F. M., Pohlman T. H., Omiecinski C. J. Expression of cytochrome P450s and microsomal epoxide hydrolase in primary cultures of human umbilical vein endothelial cells. Toxicol. Appl. Pharmacol. 1994; 124: 1
  • Heckbert S. R., Weiss N. S., Hornung S. K., Eaton D. L., Motulsky A. G. Glutathione-S-trans-ferase and epoxide hydrolase activity in human leukocytes in relation to risk of lung cancer and other smoking-related cancers. J. Natl. Cancer Inst. 1992; 84: 414
  • Gaedigk A., Spielberg S. P., Grant D. M. Characterization of the microsomal epoxide hydrolase gene in patients with anticonvulsant adverse drug reactions. Pharmacogenetics 1994; 4: 142
  • Hassett C., Aicher L., Sidhu J. S., Omiecinski C. J. Human microsomal epoxide hydrolase: genetic polymorphism and functional expressionin vitro of amino acid variants. Hum. Mol. Genet. 1994; 3: 421
  • McGlynn K. A., Rosvold E. A., Lustbader E. D., Hu Y., Clapper M. L., Zhou T., Wild C. P., Xia X. L., Baffoe-Bonnie A., Ofori-Adjei D., et al. Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B. Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 2384
  • Lind C., Cadenas E., Hochstein P., Ernster L. DT-Diaphorase: purification, properties and function. Methods Enzymoi 1990; 186: 287
  • Jaiswal A. K. Human NAD(P)H: quinone oxy-doreductase (NQOI) gene structure and induction by dioxin. Biochemistry 1991; 30: 10647
  • Jaiswal A. K., McBride O. W., Adesnik M., Nebert D. W. Human dioxin-inducible cytosolic NAD(P)H:menadione oxidoreductase. J. Biol. Chem. 1988; 263: 13572
  • Traver R. D., Tetsuro H., Danenberg K. D., Stadlbauer T. H. W., Danenberg P. V., Ross D., Gibson N. W. NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mytomycin sensitivity. Cancer Res. 1995
  • Rosvold E. A., McGlynn K. A., Lustbader E. D., Buetow K. H. Identification of an NAD(P)H:qui-none oxidoreductase polymorphism and its association with lung cancer and smoking. Pharmacogenetics 1995; 5: 199
  • Jim C. J., Miners J. O., Burchell B., Mackenzie P. I. The glucuronidation of hydroxylated metabolites of benzo[a]pyrene and 2-acetylaminofluorene by cDNA-expressed human UDP glucuronosyltrans-ferases. Carcinogenesis 1993; 14: 2637
  • Moghrabi N., Clarke D. J., Burchell B., Boxer M. Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar type I: implication in carrier detection and prenatal diagnosis. Am. J. Hum. Genet. 1993; 53: 722
  • Patel M., Tang B. K., Kalow W. (S)Oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7. Pharmacogenetics 1995; 5: 43
  • Bonicke R., Reif W. Enzymatic inactivation of isonicotinic acid hydrazide in humans and animals. Arch. Exp. Pathol. Pharmakol. 1953; 220: 321
  • Bonicke R., Lisboa B. P. On the inherited basis of intraindividual constancy of isoniazid elimination in man (studies of monozygotic and dizygotic twins). Naturwissenschaften 1957; 44: 314
  • Weber W. W., Hein D. W. N-acetylation pharmacogenetics. Pharmacol. Rev. 1985; 37: 25
  • Hickman D., Sim E. N-acetyltransferase polymorphism. Comparison of phenotype and genotype in humans. Biochem. Pharmacol 1991; 42: 1007
  • Blum M., Grant D. M., McBride O. W., Heim M., Meyer U. A. Human arylamine N-acetyl-transferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 1990; 9: 193
  • Ohsako S., Deguchi T. Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver. J. Biol. Chem. 1990; 265: 4630
  • Ebisawa T., Deguchi T. Structure and restriction fragment length polymorphism of genes for human liver arylamine N-acetyltransferase. Biochem. Biophys. Res. Commun. 1991; 177: 1252
  • Bell D. A., Taylor J. A., Butler M. A., Stephens E. A., Wiest J., Brubacker L. H., Kadlnbar F. F., Lucier G. W. Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new acetylator allele common in African-Americans. Carcinogenesis 1993; 14: 1689
  • Abe M., Deguchi T., Suzuki T. The structure and characteristics of a fourth allele of polymorphic n-acetyltransferase gene found in the Japanese population. Biochem. Biophys. Res. Commun. 1993; 191: 811
  • Vatsis K. P., Weber W. W., Bell D. A., Dupret J. M., Evans D. A. P., Grant D. M., Hein D. W., Lin H. J., Meyer U. A., Relling M. V., et al. Nomenclature for N-acetyltransferases. Pharmacogenetics 1995; 5: 1
  • Rothman N., Hayes R. B., Bi W., Caporaso N., Broly F., Woosley R. L., Yin S., Feng P., You X., Meyer U. A. Correlation between N-acetyltransferase activity and NAT2 genotype in Chinese males. Pharmacogenetics 1993; 3: 250
  • Cascorbi I., Drakoulis N., Brockmtiller J., Maurer A., Sperling K., Roots I. Arylamine N-acetyltransferase(NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am. J. Hum. Genet. 1995; 57: 581
  • Cartwright R. A. Epidemiological studies on N-acetylation and C-center ring oxidation in neoplasia. Genetic Variability in Responses to Chemical Exposure, G. S. Omenn, H. V. Gelboin. Cold Spring Harbor Laboratory, New York 1984; 359
  • Karakaya A. E., Cok I., Sardas S., Gogus O. S. N-Acetyltransferase phenotype of patients with bladder cancer. Hum. Toxicol 1989; 5: 333
  • Hayes R., Bi W., Rothman N., Broly F., Caporaso N., Feng P., You X., Yin S., Woosley R. L., Meyer U. A. N-Acetylation phenotype and genotype and risk of bladder cancer in benzidine-exposed workers. Carcinogenesis 1993; 14: 675
  • Lang N. P., Butler M. A., Massengill J. P., Lawson M., Stotts R. C., Hauer-Jensen M., Kadlubar F. F. Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiol. Biomark. Prev. 1994; 3: 675
  • Vatsis K. P., Martell K. J., Weber W. W. Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc. Natl. Acad. Sci. U.S.A. 1991; 88: 6333
  • Weber W. W., Vatsis K. P. Individual variability in p-aminobenzoic acid N-acetylation by human /V-acetyltransferase (NAT 1) or peripheral blood. Pharmacogenetics 1993; 3: 209
  • Bell D. A., Badawi A. F., Lang N. P., Ilett K. F., Kadlubar F. F., Hirvonen A. Polymorphism in the N-acetyltransferase 1(NAT1) polyadenylation signal: association ofNAT110 allele with higherN-acetylation activity in bladder and colon tissue. Cancer Res. 1995; 55: 5226
  • Badawi A. F., Hirvonen A., Bell D. A., Lang N. P., Kadlubar F. F. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer Res. 1995; 55: 5230
  • Bell D. A., Stephens E. A., Castranio T., Umbach D. M., Watson M., Deakin M., Elder J., Hendrickse C., Duncan H., Strange R. C. Polyadenylation polymorphism in the acetyltransferase I gene(NAT]) increases risk of colorectal cancer. Cancer Res. 1995; 55: 3537
  • Hein D. W., Doll M. A., Rustan T. D., Gray K., Feng Y., Ferguson R. J., Grant D. M. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 1993; 14: 1633
  • Vineis P., Bartsch H., Caporaso N., Harrington A. M., Kadlubar F. F., Landi M. T., Malaveille C., Shields P. G., Skipper P., Talaska G., et al. Genetically-based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens. Nature (London) 1994; 369: 154
  • Daniel V. Glutathione S-transferases: gene structure and regulation of expression. Crit. Rev. Biochem. Mol. Biol 1993; 28: 173
  • Mannervik B., Danielson U. H. Glutathione transferases – structure and catalytic activity. CRC Crit. Rev. Biochem. 1988; 23: 281
  • Awasthi Y. C., Sharma R., Singhal S. S. Human glutathione S-transferases. Int. J. Biochem. 1994; 26: 295
  • Zhong S., Wyllie A. H., Barnes D., Wolf C. R., Spurr N. K. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 1993; 14: 1821
  • Fryer A. A., Zhao L., Alldersea J., Pearson W. R., Strange R. C. Use of site-directed mutagenesis of allele-specific PCR primers to identify the GSTM1 A, GSTM1 B, GSTM1 A,B and GSTM1 null polymorphisms at the glutathione S-transferase, GSTM1 locus. Biochem. J. 1993; 295: 313
  • Bell D. A., Taylor J. A., Paulson D. F., Robertson C. N., Mohler J. L., Lucier G. W. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-trans-ferase Ml (GSTM1) that increases susceptibility to bladder cancer. J Natl. Cancer Inst. 1993; 85: 1159
  • Nakajima T., Elovaara E., Anttila S., Hirvonen A., Camus A. M., Hayes J. D., Ketterer B., Vainio H. Expression and polymorphism of glutathione S-transferase in human lungs: risk factors in smoking-related lung cancer. Carcinogenesis 1995; 16: 707
  • Fryer A. A., Zhao L., Alldersea J., Boggild M. D., Perrett C. W., Clayton R. N., Jones P. W., Strange R. C. The glutathione S-transferases: polymerase chain reaction studies on the frequency of the GSTM1 0 genotype in patients with pituitary adenomas. Carcinogenesis 1993; 14: 563
  • Anttila S., Hirvonen A., Husgafvel-Pursiainen K., Karjalainen A., Nurminen T., Vainio H. Combined effect of CYP1A1 inducibility andGSTMl polymorphism on histological type of lung cancer. Carcinogenesis 1994; 15: 1133
  • Hirvonen A., Husgafvel-Pursiainen K., Anttila S., Vainio H. The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung. Carcinogenesis 1993; 14: 1479
  • Ketterer B., Harris J. M., Talaska G., Meyer D. J., Pemble S. E., Taylor J. B., Lang N. P., Kadlubar F. F. The human glutathione S-transferase supergene family, its polymorphism, and its effects on susceptibility to lung cancer. Em: Health Perspect. 1992; 98: 87
  • London S. J., Daly A. K., Cooper J., Navidi W. C., Carpenter C. L., Idle J. R. Polymorphism of glutathione S-transferase Ml and lung cancer risk among African-Americans and Caucasians in Los Angeles county, California. J. Natl. Cancer Inst. 1995; 87: 1246
  • Trizna Z., Dayman G., Spitz M. R., Briggs K. L., Goepfert H. Glutathione S-transferase genotypes as risk factors for head and neck cancer. Am. J. Surgery 1995; 170: 499
  • Heagerty A. H. M., Fitzgerald D., Smith A., Bowers B., Jones P., Fryer A. A., Zhao L., Alldersea J., Strange R. C. Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous tumours. Lancet 1994; 343: 266
  • Lafuente A., Molina R., Palou J., Castel T., Moral A., Trias M., MMM Group. Pheno-type of glutathione S-transferase Mu (GSTM1) and susceptibility to malignant melanoma. Br. J. Cancer. 1995; 72: 324
  • Lin H. J., Han C. Y., Bernstein D. A., Hsiao W., Lin B. K., Hardy S. Ethnic distribution of the glutathione transferase Mu 1–1(GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility. Carcinogenesis 1994; 15: 1077
  • Nakachi K., Imai K., Hayashi S. L, Kawajiri K. Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res. 1993; 53: 2994
  • Kawajiri K., Watanabe J., Eguchi H., Hayashi S. L. Genetic polymorphisms of drug-metabolizing enzymes and lung cancer susceptibility. Pharmacogenetics 1995; 5: S70
  • Kihara M., Kihara M., Noda K. Lung cancer-risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure. Carcinogenesis 1994; 15: 415
  • Kihara M., Noda K., Kihara M. Distribution of GSTM1 null genotype in relation to gender, age and smoking status in Japanese lung cancer patients. Pharmacogenetics 1995; 5: S74
  • Hirvonen A., Nylund L., Kociba P., Husgafvel-Pursiainen K., Vainio H. Modulation of urinary mutagenicity by genetically determined carcinogen metabolism in smokers. Carcinogenesis 1994; 15: 813
  • Anttila S., Luostarinen L., Hirvonen A., Elovaara E., Karjalainen A., Nurminen T., Hayes J. D., Vainio H., Ketterer B. Pulmonary expression of glutathione S-transferase M3 in lung cancer patients: association withGSTM I polymorphism, smoking, and asbestos exposure. Cancer Res. 1995; 55: 3305
  • Pemble S., Schroeder K. R., Spencer S. R., Meyer D. J., Hallier E., Bolt H. M., Ketterer B., Taylor J. B. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterisation of a genetic polymorphism. Biochem. J. 1994; 300: 271
  • Elexpuru-Camiruaga J., Buxton N., Kandula V., Dias P., Campbell D., McIntosh J., Broome J., Jones P., Inskip A., Alldersea J., et al. Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase (GSTT1 and GSTM 1) and cytochrome P-450 (CYP2D6) loci. Cancer Res. 1995; 55: 4237
  • Warwick A., Sarhanis P., Redman C., Pemble S., Taylor J. B., Ketterer B., Jones P., Alldersea J., Gilford J., Yengi L., et al. Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM 1, CYP2D6 and smoking. Carcinogenesis 1994; 15: 2841
  • Butler M. A., Iwasaki M., Guengerich F. P., Kadlubar F. F. Human P450PA (P-450–1A2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxida-tion of carcinogenic amines. Proc. Natl. Acad. Sci. U.S.A. 1989; 86: 7696
  • Crespi C. L., Penman B. W., Gelboin H. V., Gonzalez F. J. A tobacco smoke-derived nitrosamine. 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone, is activated by multiple cytochrome P450s including the polymorphic cytochrome P4502D6. Carcinogenesis 1991; 12: 1197
  • Ikeya K., Jaiswal A. K., Owens R. A., Jones J. E., Nebert D. W., Kimura S. HumanCYP1A2. Sequence, gene structure, comparison with the mouse and rat orthologous gene, and genetic differences in liver 1A2 mRNA concentrations. Mol. Endocrinol 1989; 3: 1399
  • Yamazaki H., Mimura M., Oda Y., Inui Y., Shiraga T., Iwasaki K., Guengerich F. P., Shimada T. Roles of different forms of cytochrome P450 in the activation of the promutagen 6-aminochry-sene to genotoxic metabolites in human liver microsomes. Carcinogenesis 1993; 14: 1271
  • Kadlubar F. F., Butler M. A., Kaderlik K. R., Chou H. C., Lang N. P. Polymorphisms for aromatic amine metabolism in humans: relevance for human carcinogenesis. Environ. Health Perspect. 1992; 98: 69
  • Shimada T., Yun C. H., Hiroshi Y., Gautier J. C., Beaune P. H., Guengerich F. P. Characterization of human lung microsomal cytochrome P4501 Al and its role in the oxidation of chemical carcinogens. Mol. Pharmacol 1992; 41: 856
  • Butler M. A., Lang N. P., Young J. F., Caporaso N. E., Vineis P., Hayes R. B., Teitel C. H., Massengill J. P., Lawsen M. F., Kadlubar F. F. Determination of CYP1A2 and acetyltransferase phenotype in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 1992; 2: 116
  • Kapitulnik J., Poppers P. J., Conney A. H. Comparative metabolism of benzo(a)pyrene and drugs in human liver. Clin. Pharmacol. Ther. 1977; 21: 166
  • Miles J. S., McLaren A. W., Forrester L. M., Glancey M. J., Lang M. A., Wolf C. R. Identification of the human liver cytochrome P-450 responsible for coumarin 7-hydroxylase activity. Biochem. J. 1990; 267: 365
  • Yamano S., Tatsuno J., Gonzalez F. J. TheCYP2A3 gene product catalyzes coumarin 7-hydroxy-lation in human liver microsomes. Biochemistry 1990; 29: 1322
  • Maurice M., Emiliani S., Dalet-Beluche I., Derancourt J., Lange R. Isolation and characterization of a cytochrome P-450 of the IIA subfamily from human liver microsomes. Eur. J. Biochem. 1991; 200: 365
  • Fernandez-Salguero P., Hoffman S. M. G., Cholerton S., Mohrenweiser H., Raunio H., Rautio A., Pelkonen O., Huang J. D., Evans W. E., Idle J. R., et al. A genetic polymorphism in coumarin 7-hydroxylation: sequence of the humanCYP2A genes and identification of variantCYP2A6 alleles. Am. J. Hum. Genet. 1995; 57: 651
  • Ding X., Coon M. J. Purification and characterization of two unique forms of cytochrome P450 from rabbit nasal microsomes. Biochemistry 1988; 27: 8330
  • Fernandez-Salguero P., Gonzalez F. J. TheCYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis. Pharmacogenetics 1995; 5: SI23
  • Bale A. E., Mitchell A. L., Gonzalez F. J., McBride O. W. Localization ofCYP2F1 by multipoint linkage analysis and pulse-field gel electrophoresis. Genomics 1991; 10: 284
  • Ged C., Umbenhauer D. R., Bellew T. M., Bork R. W., Srivastava P. K., Shinriki N., Lloyd R. S., Guengerich F. P. Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxy-lase. Biochemistry 1988; 27: 6929
  • Inoue K., Inazawa J., Suzuki Y., Shimada T., Yamazaki H., Guengerich F. P., Abe T. Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1. Jpn. J. Hum. Genet. 1994; 39: 337
  • Kupfer A., Preisig R. Pharmacogenetics of mephenytoin: new drug hydroxylation polymorphism in man. Eur. J. Clin. Pharmacol 1984; 26: 753
  • Goldstein J. A., Faletto M. B., Romkes-Sparks M., Sullivan T., Kitareewan S., Raucy J. L., Lasker J. M., Ghanayem B. I. Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxy-lase in humans. Biochemistry 1994; 33: 1743
  • de Morais S. M., Wilkinson G. R., Blaisdell J., Nakamura K., Meyer U. A., Goldstein J. A. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J. Biol Chem. 1994; 269: 15419
  • Wrighton S. A., Stevens J. C., Becker G. W., YandenBranden M. Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation. Arch. Biochem. Biophys. 1993; 306: 240
  • Goldstein J. A., de Morais S. M. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 1994; 4: 285
  • Brockmoller J., Rost K. L., Gross D., Schenkel A., Roots I. Phenotyping of CYP2C19 with enantio-specific HPLC-quantification of R- and S-mephenytoin and comparison with the intron4/exon5 G-A-splice site mutation. Pharmacogenetics 1995; 5: 80
  • Adedoyin A., Prakash C., O'Shea D., Blair I. A., Wilkinson G. R. Stereoselective disposition of hexobarbital and its metabolites: relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. Pharmacogenetics 1994; 4: 27
  • Yasumori T., Li Q. H., Yamazoe Y., Ueda M., Tsuzuki T., Kato R. Lack of low Km diazepam N-demethylase in livers of poor metabolizers for S-mephenytoin 4'-hydroxylation. Pharmacogenetics 1994; 4: 323
  • Yasumori T., Nagata K., Yang S. K., Chen L. S., Murayama N., Yamazoe Y., Kato R. Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N-demethylation in the substrate concentration-dependent manner. Pharmacogenetics 1993; 3: 291
  • Cresteil T., Monsarrat B., Alvinerie P., Treluyer J. M., Vieira I., Wright M. Taxol metabolism by human liver microsomes: identification of cytochrome P450 isozymes involved in its biotransformation. Cancer Res. 1994; 54: 386
  • Rahman A., Korzekwa K. R., Grogan J., Gonzalez F. J., Harris J. W. Selective biotransformation of taxol to 6a-hydrotaxol by human cytochrome P450 2C8. Cancer Res. 1994; 54: 5543
  • Watkins P. B. Noninvasive tests of CYP3A enzymes. Pharmacogenetics 1994; 4: 171
  • Breimer D. D., Schellens J. M. H., Soons P. A. Nifepidine: variability in its kinetics and metabolism in man. Pharmacol. Ther. 1989; 44: 445
  • Fleming C. M., Branch R. A., Wilkinson G. R., Guengerich F. P. Human liver microsomal N-hydroxylation of dapsone by cytochrome P4503A4. Mol Pharmacol. 1992; 41: 975
  • Watkins P. B., Murray S. A., Winkelman L. G., Heuman D. M., Wrighton S. A., Guzelian P. S. Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochrome P450. J. Clin. Invest. 1989; 83: 688
  • Kolars J. C., Lown K. S., Schmiedlin-Ren P., Ghosh M., Fang C., Wrighton S. A., Merion R. M., Watkins P. B. CYP3A gene expression in human gut epithelium. Pharmacogenetics 1994; 4: 247
  • Daly A. K., Salh B. S., Bilton D., Allen J., Knight A. D., Webb A. K., Braganza J. M., Idle J. R. Deficient nifepidine oxidation: a rare inherited trait associated with cystic fibrosis kindreds. Pharmacogenetics 1992; 2: 19
  • Furlong C. E., Costa L. G., Hassett C., Richter R. J., Sundstrom J. A., Adler D. A., Disteche C. M., Omiecinski C. J., Chapline C., Crabb J. W. Human and rabbit paraoxonases: purification. cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification. Chem. Biol. Interact. 1993; 87: 35
  • Tsui L. C., Buchwald M., Barker D., Braman J. C., Knowlton R., Schumm J. W., Eiberg H., Mohr J., Kennedy D., Plavsic N. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science 1985; 230: 1054
  • Knowlton R. G., Cohen-Haguenauer O., Van Cong N., Frezal J., Brown V. A., Barker D., Braman J. C., Schumm J. W., Tsui L. C., Buchwald M. A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7. Nature, (London) 1985; 318: 380
  • Adkins S., Gan K. N., Mody M., La Du B. N. Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am. J. Hum. Genet 1993; 52: 598
  • Karakaya A., Suzen S., Sardas S., Karakaya A. E., Vural N. Analysis of the serum paraoxonase/arylesterase polymorphism in a Turkish population. Pharmacogenetics 1991; 1: 58
  • Roy A. C., Saha N., Tay J. S., Ratnam S. S. Serum paraoxonase in three populations of Southeast Asia. Hum. Hered. 1991; 41: 265
  • Clavel J., Hemon D. Fundamentals of case-control studies. Pharmacogenetics 1993; 3: 160
  • Lander E. S., Schork N. J. Genetic dissection of complex traits. Science 1994; 265: 2037
  • Lifton R. P., Jeunemaitre X. Finding genes that cause human hypertension. J. Hypertens. 1993; 11: 231
  • Jeunemaitre X., Rigat B., Charru A., Houot A. M., Soubrier F., Corvol P. Sib pair linkage analysis of renin gene haplotypes in human essential hypertension. Hum. Genet. 1992; 88: 301
  • Jeunemaitre X., Soubrier F., Kotelevtsev Y. V., Lifton R. P., Williams C. S., Charru A., Hunt S. C., Hopkins P. N., Williams R. R., Lalouel J. M. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71: 169
  • Pritchard L. E., Kawaguchi Y., Reed P. W., Copeman J. B., Davies J. L., Barnett A. H., Bain S. C., Todd J. A. Analysis of the CD3 gene region and type 1 diabetes: application of fluorescence-based technology to linkage disequilibrium mapping. Hum. Mol. Genet. 1995; 4: 197
  • Davies J. L., Kawaguchi Y., Bennett S. T., Copeman J. B., Cordell H. J., Pritchard L. E., Reed P. W., Gough S. C., Jenkins S. C., Palmer S. M. A genome-wide search for human type 1 diabetes susceptibility genes. Nature, (London) 1994; 371: 130
  • Reed P. W., Davies J. L., Copeman J. B., Bennett S. T., Palmer S. M., Pritchard L. E., Gough S. C., Kawaguchi Y., Cordell H. J., Balfour K. M. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nature Genet. 1994; 7: 390
  • Williams R. J. Biochemical Individuality. John Wiley & Sons, New York 1956
  • Nelson D. B., Nerbert D. W., et al. Pharmacogenetics 1996; 6: 1
  • Micka, et al. Pharmacogenetics, in press
  • Daly A. K., et al. Pharmacogenetics 1996; 6: 193
  • Meyer U. A., personal communication
  • Shertzer H. G., Nerbert D. W., unpublished data

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