Abstract
Genetic polymorphisms with functional effects occur in many of the genes encoding drug metabolizing enzymes and are an important cause of adverse drug reations. Recent advances in the understanding of the molecular genetics of drug-metabolizing enzymes, particularly the cytochromes P450, has enabled the molecular basis of several polymorphisms to be elucidated and genotyping assays using the polymerase chain reaction to be developed. Polymorphisms in this category include those in the cytochrome P450 genes CYP2D6, CYP2C19, CYP2A6, CYP2C9 and CYP2E1, the glutathione S-transferase genes GSTM1 and GSTT1 and the N-acetyltransferase gene NAT2. The molecular basis and impotance to drug metabolism of the various polymorphisms as well as evidence for the existence of polymorphisms in other genes encoding drug-metabolizing enzymes such as the UDP-glucuronosyltransferases, the sulphotransferases and the methyltransferases are discussed.
Similar content being viewed by others
Abbreviations
- DHEA ST :
-
Dehydroepiandrosterone sulphotransferase
- EST :
-
Oestrogen sulphotransferase
- TL ST :
-
Thermolabile sulphotransferase
- TS ST :
-
Thermostable sulphotransferase
References
Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL (1977) Polymorphic hydroxylation of debrisoquine in man. Lancet 11:584–586
Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 17:153–155
Inaba T, Otton SV, Kalow W (1980) Deficient metabolism of debrisoquine and sparteine. Clin Pharmacol Ther 27:547–549
Dayer P, Gasser R, Gut J, Kronbach T, Robertz GM, Eichelbaum M, Meyer UA (1984) Characterization of a common genetic defect of cytochrome P450 function (debrisoquinesparteine type polymorphism). Biochem Biophys Res Commun 125:374–380
Cholerton S, Daly AK, Idle JR (1992) The role of individual human cytochromes P450 in drug metabolism and clinical response. Trends Pharmacol Sci 13:434–438
Gonzalez FJ, Idle JR (1994) Pharmacogenetic phenotyping and genotyping. Present status and future potential. Clin Pharmacokinet 26:59–70
Evans DAP (1993) Genetic factors in drug therapy. Clinical and molecular pharmacogenetics. Cambridge University Press, Cambridge
Daly AK, Cholerton S, Gregory W, Idle JR (1993) Metabolic polymorphisms. Pharmacol Ther 57:129–160
Hall MCS, Gregory WL, Idle JR (1994) Pharmacogenetics: can the therapeutic key objective be accomplished? In: Seymour CA, Weetman RA (eds) Horizons in medicine, vol 5. Blackwell, London, pp 79–91
Kimura S, Umeno M, Skoda RC, Meyer UA, Gonzalez FJ (1989) The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of a polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am J Hum Genet 45:889–905
Daly AK, Armstrong M, Monkman SC, Idle ME, Idle JR (1991) The genetic and metabolic criteria for the assignment of debrisoquine hydroxylation (cytochrome P450IID6) phenotypes. Pharmacogenetics 1:33–41
Broly F, Gaedigk A, Heim M, Eichelbaum M, Morike K, Meyer UA (1991) Debrisoquine/sparteine hydroxylation genotype and phenotype: analysis of common mutations and alleles of CYP2D6 in a European population. DNA Cell Biol 10:545–558
Saxena R, Shaw GL, Relling MV, Frame JN, Moir DT, Evans WE, Caporaso N, Weiffenbach B (1994) Identification of a new variant CYP2D6 single base pair deletion in exon 3 and its association with the poor metabolizer phenotype. Hum Mol Genet 3:923–926
Evert B, Griese E-U, Eichelbaum M (1994) A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine to proline exchange is associated with the poor metabolizer phenotype of sparteine. Naunyn-Schmiedebergs Arch Pharmacol 350:434–439
Yokota H, Tamura S, Furuya H, Kimura S, Watanbe M, Kanazawa I, Kondo I, Gonzalez FJ (1993) Evidence for a new variant allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism. Pharmacogenetics 3:256–263
Wang S-L, Huang J-D, Lai M-D, Liu B-H, Lai M-L (1993) Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 53:410–418
Johansson I, Oscarson M, Yue Q-Y, Bertilsson L, Sjoqvist F, Ingelman-Sundberg M (1994) Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxyalation. Mol Pharmacol 46:452–259
Kagimoto M, Heim M, Kagimoto K, Zeugin T, Meyer UA (1990) Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolisers of debrisoquine. J Biol Chem 265:17209–17214
Evans WE, Relling MV, Rahman A, McLeod HL, Scott EP, Lin J-S (1993) Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans. J Clin Invest 91:2150–2154
Bertilsson L, Dahl M-L, Sjoqvist F, Aberg-Wistedt A, Humble M, Johansson I, Lundqvist E, Ingelman-Sundberg M (1993) Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet 341:63
Johansson I, Lundqvist E, Bertilsson L, Dahl M-L, Sjoqvist F, Ingelman-Sundberg M (1993) Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci USA 90:11825–11829
Agundez JAG, Ledesma MC, Ladero JM, Benitez J (1995) Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population. Clin Pharmacol Ther 57:265–269
Shah RR, Oates NS, Idle JR, Smith RL, Lockhart JDF (1982) Impaired oxidation of debrisoquine in patients with perhexilene neuropathy. BMJ 284:295–299
Sindrup SH, Brosen K, Bjerring K, Arendt-Nielsen L, Larsen V, Angelo HR, Gram LF (1991) Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. Clin Pharmacol Ther 49:686–693
Persson K, Sjostrom S, Sigurdardottir I, Molnar V, Hammar-lundudenaes M, Rane A (1995) Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in 10 extensive metabolizers and one poor metabolizer of dextromethorphan. Br J Clin Pharmacol 39:182–186
Siddoway LA, Thompson KA, McAllister CB, Wang T, Wilkinson GR, Roden DM, Woosley RL (1987) Polymorphism of propafenone metabolism in man. Circulation 75:785–791
Dahl M-L, Bertilsson L (1993) Genetically variable metabolism of antidepressants and neuroleptic drugs in man. Pharmacogenetics 3:61–70
Ayesh R, Idle JR, Ritchie JC, Crothers MJ, Hetzel MR (1984) Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature 311:169–170
Kaisary A, Smith P, Jacqz E, McAllister CB, Wilkinson GR, Ray WA, Branch RA (1987) Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors. Cancer Res 47:5488–5493
Armstrong M, Daly AK, Cholerton S, Bateman DN, Idle JR (1992) Mutant debrisoquine hydroxylation genes in Parkinson's disease. Lancet 339:1017–1018
Smith CAD, Gough AC, Leigh PN, Summers BA, Harding AE, Maranganore DM, Sturman SG, Schapira AHV, Williams AC, Spurr NK, Wolf CR (1992) Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease. Lancet 339:1375–1377
Wolf CR, Smith CAD, Gough AC, Moss JE, Vallis KA, Howard G, Carey FJ, Mills K, McNee W, Carmichael J, Spurr NK (1992) Relationship between the debrisoquine hydroxylase polymorphism and cancer susceptibility. Carcinogenesis 13:1035–1038
Tefre T, Daly AK, Armstrong M, Leathart JBS, Idle JR, Brogger A, Borresen A-L (1994) Genotyping of the CYP2D6 gene in Norwegian lung cancer patients and controls. Pharmacogenetics 4:47–57
Kupfer A, Dick B, Preisig R (1982) A new drug hydroxylation polymorphism in man: the incidence of mephenytoin hydroxylation deficient phenotypes in an European population study. Naunyn-Schmiedebergs Arch Pharmacol 321:33
Wilkinson GR, Guengerich FP, Branch RA (1989) Genetic polymorphisms of S-mephenytoin hydroxylation. Pharmacol Ther 43:53–76
Meier UT, Meyer UA (1987) Genetic polymorphism of human cytochrome P450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a fuctionally altered cytochrome P450 isozyme as cause of the genetic deficiency. Biochemistry 26:8466–8474
Umbenhauer DR, Martin MV, Lloyd RS, Guengerich FP (1987) Cloning and sequence determination of a complementary DNA related to human liver microsomal cytochrome P450 S-mephenytoin 4-hydroxylase. Biochemistry 26:1094–1099
Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (1991) Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. Biochemistry 30:3247–3255
Brian WR, Srivastava PK, Umbenhauer DR, Lloyd RS, Guengerich FP (1989) Expression of a human liver cytochrome P450 protein with tolbutamide hydroxylase activity in Saccharomyces cerevisiae. Biochemistry 28:4993–4999
Furuya H, Meyer UA, Gelboin HV, Gonzalez FJ (1991) Polymerase chain reaction directed identification, cloning and quantification of human CYP2C18 mRNA. Mol Pharmacol 40:375–382
Wrighton SA, Stevens JC, Becker GW, VandenBranden M (1993) Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4′-hydroxylation. Arch Biochem Biophys 306:240–245
Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM, Ghanayem BI (1994) Evidence that CYP2C19 is the major (S)-mephenytoin 4′-hydroxylase in humans. Biochemistry 33:1743–1752
de Morais SMF, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA (1994) Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 46:594–598
de Morais SMF, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA (1994) The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 269:15419–15422
Goldstein JA, de Morais SMF (1994) Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 4:285–300
Brosen K, de Morais SMF, Meyer UA, Goldstein JA (1995) A multifamily study on the relationship between CYP2C19 genotype and the S-mephenytoin oxidation polymorphism. Pharmacogenetics (in press)
Rost KL, Brosicke H, Brockmoller J, Scheffler M, Helge H, Roots I (1992) Increase of cytochrome P-450 1A2 activity by omeprazole: evidence by the 13C[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther 52:170–180
Ward SA, Helsby NA, Skjelbo E, Brosen K, Gram LF, Breckenbridge AM (1991) The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation phenotype-a panel study. Br J Clin Pharmacol 31:689–692
Scott J, Poffenbarger PL (1978) Pharmacogenetics of tolbutamide metabolism in humans. Diabetes 28:41–51
Relling MV, Aoyama T, Gonzalez FJ, Meyer UA (1990) Tolbutamide and mephenytoin hydroxyation by human cytochrome P450s in the CYP2C subfamily. J Pharmacol Exp Ther 152:442–447
Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ (1987) cDNA and amino acid sequences of two members of the human P450IIC gene subfamily. Nucl Acids Res 15:10053–10054
Yasumori T, Kawano S, Nagata K, Shimada M, Yamazoe Y, Kalo R (1987) Nucleotide sequence of a human liver cytochrome P450 related to the rat male-specific form. J Biochem (Tokyo) 102:493–501
Meehan RR, Gosden JR, Rout D, Hastie ND, Friedberg T, Adesnik M, Buckland R, van Heyningen V, Fletcher J, Spurr NK, Sweeney J, Wolf CR (1988) Human cytochrome P450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10. Am J Hum Genet 42:26–37
Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR (1994) Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics 4:39–42
Veronese ME, Doecke CJ, Mackenzie PI, McManus ME, Miners JO, Rees DLP, Gasser R, Meyer UA, Birkett DJ (1993) Site-directed mutation studies of human liver cytochrome P-450 isoenzymes in the CYP2C subfamily. Biochem J 289:533–538
Veronese ME, Mackenzie PI, Doecke CJ, McManus ME, Miners JO, DJ Birkett (1991) Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem Biophys Res Commun 175:1112–1118
Kaminsky LS, de Morais SMF, Faletto MB, Dunbar DA, Goldstein JA (1993) Correlation of human cytochrome P2502C substrate specificities with primary structure: warfarin as a probe. Mol Pharmacol 43:234–239
Wang S-L, Huang J-D, Lai M-D, Tsai J-J (1995) Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 5:37–42
Veronese ME, Miners JO, Rees DLP, Birkett DJ (1993) Tolbutamide hydroxylation in humans: lack of bimodality in 106 healthy subjects. Pharmacogenetics 3:86–93
Inaba T (1990) Phenytoin: pharmacogenetic polymorphism of 4′-hydroxyation. Pharmacol Ther 46:341–347
Marshall ME, Mohler JL, Edmonds K, Williams B, Butler K, Ryles M, Weiss L, Urban D, Bueschen A, Markiewicz M, Cloud G (1994) An updated review of the clinical development of coumarin (1, 2-benzopyrone) and 7-hydroxycoumarin. J Cancer Res Clin Oncol 120 [Suppl]:S39-S42
Daly AK, Cholerton S, Armstrong M, Idle JR (1994) Genotyping for polymorphisms in xenobiotic metabolism as a predictor of disease susceptibility. Environ Health Perspect 102 [Suppl 9]:55–61
McCracken NW, Cholerton S, Idle JR (1992) Cotinine formation by cDNA-expressed human cytochromes P450. Med Sci Res 20:877–878
Cholerton S, Idle ME, Vas A, Gonzalez FJ, Idle JR (1992) Comparison of a novel thin-layer chromatographic-flourescence detection method with a spectrofluorometric method for the determination of 7-hydroxycoumarin in human urine. J Chromatogr 575:325–330
Rautio A, Kraul H, Kojo A, Salmela E, Pelkonen O (1992) Interindividual variation of coumarin 7-hydroxylase in healthy volunteers. Pharmacogenetics 2:227–233
Yamano S, Tatsuno J, Gonzalez FJ (1990) The CYP2A3gene product catalyses coumarin 7-hydroxylation in human liver microsomes. Biochemistry 29:1322–1329
Fernandez-Salguero P, Huffman SMG, Cholerton S, Mohrenweiser H, Raunio H, Pelkonen O, Huang J, Evans WE, Idle JR, Gonzalez FJ (1995) A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. Am J Hum Genet 57:651–660
Guengerich FP, Kim D-H, Iwasaki M (1991) Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4:168–179
Patten CJ, Thomas PE, Guy RL, Lee M, Gonzalez FJ, Guengerich FP, Yang CS (1993) Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics. Chem Res Toxicol 6:511–518
Kim RB, O'Shea D, Wilkinson GR (1994) Relationship in healthy subjects between CYP2E1 genetic polymorphisms and the 6-hydroxylation of chlorzoxaazone: a putative measure of CYP2E1 activity. Pharmacogenetics 4:162–165
Vesell ES, DeAngelo Seaton T, A-Rahim YI (1995) Studies on interindividual variations of CYP2E1 using chlorzoxazone as an in vivo probe. Pharmacogenetics 5:53–57
Kim RB, O'Shea D, Wilkinson GR (1995) Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. Clin Pharmacol Ther 57:645–655
Carriere V, Goasduff T, Ratanasavanh D, Morel F, Gautier JC, Guillouzo A, Beaune P, Berthou F (1993) Both cytochromes P450 2E1 and 1A2 are involved in the metabolism of chlorzoxazone. Chem Res Toxicol 6:852–857
Ono S, Hatanaka T, Hotta H, Tsutsui M, Satoh T, Gonzalez FJ (1995) Chlorzoxazone is metabolized by human CYP1A2 as well as by CYP2E1. Pharmacogenetics 5:141–148
Yamazaki H, Guo Z, Guengerich FP (1995) Selectivity of cytochrome P4502E1 in chlorzoxazone 6-hydroxylation. Drug Metab Dispos 23:438–440
McBride OW, Umeno M, Gelboin HV, Gonzalez FJ (1987) A Taq I polymorphism in the human P450IIE1 gene on chromosome 10 (CYP2E). Nucleic Acids Res 15:10071
Kelsell DP, Wolf CR, Spurr NK (1990) An XmnI RFLP detected with a probe for the CYP2E gene locus on chromosome 10. Nucleic Acids Res 18:3111
Hayashi S, Watanabe J, Kawagiri K (1991) Genetic polymorphisms in the 5′-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem 110:559–565
Uematsu F, Kikuchi H, Abe T, Motomiya M, Ohmachi T, Sagami I, Watanabe M (1991) MspI polymorphism of the human CYP2E gene. Nucleic Acids Res 19:5797
Kato S, Shields PG, Caporaso NE, Hoover RN, Trump BF, Sugimura H, Weston A, Harris CC (1992) Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk. Cancer Res 52:6712–6715
Uematsu F, Kikuchi H, Motomiya M, Abe T, Sagami I, Ohmachi T, Wakui A, Kanamaru R, Watanabe M (1991) Association between restriction fragment polymorphism of the human P450IIE1 gene and susceptibility to lung cancer. Jpn J Cancer Res 82:254–256
Kellerman G, Shaw CR, Luyten-Kellerman M (1973) Aryl hydrocarbon hydroxylase inducibility and bronchogenic carcinoma. New Eng J Med 289:934–937
Kouri RE, McKinney CE, Slomiany DJ, Snodgrass DR, Wray NP, McLemore TL (1982) Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analysed in cryopreserved lymphocytes. Cancer Res 42:5030–5037
Fujii-Kuriyama Y, Ema M, Mimura J, Matsushita N, Sogawa K (1995) Polymorphic forms of the AH receptor and induction of the CYP1A1 gene. Pharmacogenetics 5:S149-S153
Kawajiri K, Watanabe J, Eguchi H, Nakachi K, Kiyohara C, Hayashi S (1995) Polymorphisms of human Ah receptor gene are not involved in lung cancer. Pharmacogenetics 5:151–158
Hayashi S, Watanabe J, Nakachi K, Kawajiri K (1991) Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J Biochem 110:407–411
Hirvonen A, Husgafvel-Pursianinen K, Karjalainen A, Antilla S, Vainio H (1992) Point-mutational MspI and Ile-Val polymorphisms closely linked in the CYP1AI gene: lack of association with susceptibility to lung cancer in a Finnish study population. Cancer Epidemiol Biomarkers Prevention 1:485–489
Hayashi S, Watanabe J, Kawajiri K (1992) High susceptibility to lung cancer analyzed in terms of combined genotypes of P4501A1 and Mu-class glutathione 5-transferase genes. Jpn J Cancer Res 83:866–870
Butler MA, Iwasaki M, Guengerich FP, Kadlubar FF (1989) Human cytochrome P450PA (P450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci USA 86:7696–7700
Fuhr U, Doehmer J, Battula N, Wolfel C, Kudla C, Keita Y, Staib AH (1992) Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 enzymes. Biochem Pharmacol 43:225–235
Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP, Maurel P, Beaune P, Leroux JP (1993) Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol 43:827–832
Bertilsson L, Carrillo JA, Dahl ML, Llerena A, Alm C, Bondesson U, Lindstrom L, Delarubia IR, Ramos S, Benitez J (1994) Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol 38:471–473
Kalow W, Tang B-K (1991) Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 50:508–519
Relling MV, Lin J-S, Ayers GD, Evans WE (1992) Racial and gender differences in N-acetyltransferase, xanthine oxidase and CYP1A2 activities. Clin Pharmacol Ther 52:643–658
Butler MA, Lang NP, Young JF, Caporaso NE, Vineis P, Hayes RB, Teitel CH, Massengill JP, Lawsen MF, Kadlubar FF (1992) Determination of CYP1A2 and acetyltransferase phenotype in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 2:116–127
Fuhr U, Rost KL (1994) Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and saliva. Pharmacogenetics 4:109–116
Notarianni LJ, Oliver SE, Dobrocky P, Bennett PN, Silverman BW (1995) Caffeine as a metabolic probe: a comparison of the metabolic ratios used to assess CYP1A2 activity. Br J Clin Pharmacol 39:65–69
Nakajima M, Yokoi T, Mizutani M, Shin S, Kadlubar FF, Kamataki T (1994) Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 3:413–421
Watkins PB (1994) Non-invasive tests of CYP3A enzymes. Pharmacogenetics 4:171–184
Aoyama T, Yamano S, Waxman DJ, Lapenson DP, Meyer UA, Fischer V, Tyndale R, Inaba T, Kalow W, Gelboin HV, Gonzalez FJ (1989) Cytochrome P450 hPCN3, a novel cytochrome P450 IIA gene product that is differentially expressed in adult human liver. J Biol Chem 264:10388–10395
Gillam EMJ, Guo Z, Ueng Y-F, Yamazaki H, Cock I, Reilly PEB, Hooper WD, Guengerich FP (1995) Expression of cytochrome P450 3A5 in Escherichia coli: effects of 5′ modification, purification, reconstitution conditions, and catalytic activities. Arch Biochem Biophys 317:374–384
Schuetz JD, Beach DL, Guzelian PS (1994) Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics 4:11–20
Phillips IR, Dolphin CT, Clair P, Hadley MR, Hutt AJ, McCombie RR, Smith RL, Shephard EA (1995) The molecular biology of the flavin-containing monooxygenases of man. Chem-Biol Interact 96:17–32
Ayesh R, Smith RL (1990) Genetic polymorphism of trimethylamine N-oxidation. Pharmacol Ther 45:387–401
Dixon CM, Park GR, Tarbet MH (1994) Characterization of the enzyme responsible for the metabolism of sumitriptan in human liver. Biochem Pharmacol 47:1253–1257
Weyler W, Hsu YP, Breakefield XO (1990) Biochemistry and genetics of monoamine oxidase. Pharmacol Ther 47:391–417
Waring RH (1980) Variation in the human metabolism of S-carboxymethylcysteine. Eur J Drug Metab Pharmacokinet 5:49–52
Meese CO, Fischer C, Kupfer A, Wisser H, Eichelbaum M (1991) Identification of the ‘major’ polymorphic carbocysteine metabolite as S-(carboxymethylthio)-l-cysteine. Biochem Pharmacol 42:R13-R16
Beedham C (1985) Molybdenum hydroxylases as drug-metabolizing enzymes. Drug Metab Rev 96:119–156
Holmes EW, Wyngaarden JB (1989) Hereditary xanthinuria. In: Scriver SC, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw Hill, New York, pp1085–1094
La Du BN (1988) The human-serum paraoxonase arylesterase polymorphism. Am J Hum Genet 43:227–229
Lockridge O (1990) Genetic variants of human serum cholinesterase influence metabolism of the muscle relaxant succinylcholine. Pharmacol Ther 47:35–60
Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE (1993) The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet 3:73–76
Oesch F, Timms CW, Walker CH, Guenthner TM, Sparrow A, Watabe T, Wolf CR (1984) Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5:7–9
Guenthner TM (1990) Epoxide hydrolases. In: Mulder GJ (ed) Conjugation reactions in drug metabolism: an integrated approach. Taylor and Francis, London, pp 365–404
Kroetz DL, McFarland LV, Kerr BM, Levy RH (1990) Distribution of microsomal epoxide hydrolase (mEH) activity in healthy subjects. Clin Pharmacol Ther 47:160
Norris KK, DeAngelo TM, Vesell ES (1989) Genetic and environmental factors that regulate cytosolic epoxide hydrolase activity in normal human lymphocytes. J Clin Invest 84:1749–1756
Hassett C, Aicher L, Sidhu JS, Omiecinski CJ (1994) Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vivo of amino acid variants. Human Mol Genet 3:421–428
Gaedigk A, Spielberg SP, Grant DM (1994) Characterization of the microsomal epoxide hydrolase gene in patients with anticonvulsant adverse reactions. Pharmacogenetics 4:142–153
Agarwal DP, Goedde HW (1992) Pharmacogenetics of alcohol metabolism and alcoholism. Pharmacogenetics 2:48–62
Milano G, Etienne MC (1994) Potential importance of dihydropyrimidine dehydrogenase (DPD) deficiency in cancer chemotherapy. Pharmacogenetics 4:301–306
Fleming RA, Milano G, Thyss A, Etienne MC, Renee N, Schneider M, Demard F (1992) Correlation between dihydropyridine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients. Cancer Res 52:2899–2902
Berger R, Stoker-de Vries SA, Wadman SK, Duran M, Beemer FA, De Bree PK, Weits-Binnerts JJ, Penders TS, Van der Woude JK (1984) Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. Clin Chim Acta 141:227–234
Meinsma R, Fernandez-Salguero P, Van Kuilenburg ABP, Van Gennip AH, Gonzalez FJ (1995) Human polymorphism in drug metabolism: mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea. DNA Cell Biol 14:1–6
Lu Z, Zhang R, Diasio RB (1993) Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly discovered deficient patients and clinical implications in 5-flourouracil chemotherapy. Cancer Res 53:5433–5438
Evans DAP (1989) N-Acetyltransferase. Pharmacol Ther 42:157–234
Hughes HB, Biehl JP, Jones AP, Schmidt LH (1954) Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Am Rev Tuberculosis 70:266–273
Shear NH, Spielberg SP, Grant DM, Tang BK, Kalow W (1986) Differences in metabolism of sulphonamides predisposing to idiosyncratic toxicity. Ann Int Med 105:179–184
Ratain MJ, Mick R, Berezin F, Janisch L, Schilsky RL, Williams SF, Smiddy J (1991) Paradoxical relationship between acetylator phenotype and amonafide toxicity. Clin Pharmacol Ther 50:573–579
Bock KW (1992) Metabolic polymorphisms affecting activation of toxic and mutagenic arylamines. Trends Pharmacol Sci 13:223–226
Weber WW, Vatsis KP (1993) Individual variability in p-aminobenzoic acid N-acetylation by human N-acetyltransferase (NAT1) of peripheral blood. Pharmacogenetics 3:209–212
Cribb AE, Isbrucker R, Levatte T, Tsui B, Gillespie CT, Renton KW (1994) Acetylator phenotyping: the urinary caffeine metabolite ratio in slow acetylators correlates with a marker of systemic NAT1 activity. Pharmacogenetics 4:166–170
Vatsis KP, Weber WW (1993) Structural heterogeneity of Caucasian N-acetyltransferase at the NAT1 gene locus. Arch Biochem Biophys 301:71–76
Mannervik B, Danielson UH (1988) Glutathione transferases — structure and catalytic activity. CRC Crit Rev Biochem 23:281–334
Board P, Coggan M, Johnston P, Ross V, Suzuki T, Webb G (1990) Genetic heterogeneity of the human glutathione transferases: a complex of gene families. Pharmacol Ther 48:357–369
Comstock KE, Sanderson JS, Claflin G, Kenner WD (1990) GST1 gene deletion determined by polymerase chain reaction. Nucl Acids Res 18:3670
Widersten M, Pearson WR, Engstrom A, Mannervik B (1991) Heterologous expression of the allelic variant mu-class glutathione transferases mu and psi. Biochem J 276:519–524
Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB (1994) Human glutathione Stransferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271–276
Smith MT, Evans CG, Doane-Setzer P, Castro VM, Tahir MK, Mannervik B (1989) Denitrosation of 1,3-bis(2-chlorethyl)-1-nitrosourea by class μ glutathione transferases and its role in cellular resistance in rat brain tumor cells. Cancer Res 49:2621–2625
Evans CG, Bodell WJ, Ross D, Doane P, Smith MT (1986) Role of glutathione and related enzymes in brain tumor resistance to BCNU and nitrogen mustard. Proc Am Assoc Cancer Res 37:267
Seidegard J, Pero RW, Miller DG, Beattie E (1986) A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis 7:751–753
Zhong S, Howie AF, Ketterer B, Taylor J, Hayes JD, Beckett GJ, Wathen CG, Wolf CR, Spurr NK (1991) Glutathione Stranserase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis 12:1533–1537
Heckbert SR, Weiss NS, Hornung SK, Eaton DL, Motulsky AG (1992) Glutathione S-transferase and epoxide hydrolase activity in human leukocytes in relation to risk of lung cancer and other smoking-related cancers. J Natl Cancer Inst 84:414–422
Nazar-Stewart V, Motulsky AG, Eaton DL, White E, Hornung SK, Leng Z-T, Stapleton P, Weiss NS (1993) The glutathione S-transferase μ polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res 53:2313–2318
Brockmoller J, Kerb R, Drakoulis N, Nitz M, Roots I (1993) Genotype and phenotype of glutathione S-transferase class m isoenzymes μ and ψ in lung cancer patients and controls. Cancer Res 53:1004–1011
Hirvonen A, Husgafvel-Pursianinen K, Anttila S, Vainio H (1993) The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung. Carcinogenesis 14:1479–1481
Nakachi K, Imai K, Hayashi S, Kawajiri K (1993) 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 53:2944–2999
Alexandrie A, Ingelman-Sundberg M, Seidegard J, Tornling G, Rannug A (1994) Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study of host factors in relation to age at onset, gender and histologic cancer types. Carcinogenesis 15:1785–1790
Kihara M, Kihara M, Noda K (1994) Lung cancer risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure. Carcinogenesis 15:415–418
London SJ, Daly AK, Cooper J, Navidi WC, Carpenter CL, Idle JR (1995) Polymorphism of glutathione S-transferase M1 (GSTM1) and risk of lung cancer among African-Americans and Caucasians in Los Angeles county. J Natl Cancer Inst 87:1246–1253
Bell DA, Taylor JA, Paulson DF, Robertson CN, Monler JL, Lucier GW (1993) Genetic risk and carcinogen exposure: a common defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 85:1159–1164
Daly AK, Thomas DC, Cooper J, Pearson WR, Neal DE, Idle JR (1993) Homozygous deletion of the gene for glutathione S-transferase M1 in bladder cancer. BMJ 307:481–482
Lafuente A, Pujol F, Carretero P, Perez Villa J, Cuchi A (1993) Human glutathione S-transferase μ (GSTμ) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers. Cancer Lett 68:49–54
Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between the GSTM1 polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14:1821–1824
Lin HJ, Han C-Y, Bernstein DA, Hsiao W, Lin BK, Hardy S (1994) Ethnic distribution of the glutathione transferase Mu 1–1 (GSTM1) null phenotype in 1473 individuals and application to bladder cancer susceptibility. Carcinogenesis 15:1077–1081
Brockmoller J, Kerb R, Drakoulis N, Staffeldt B, Roots I (1994) Glutathione S-transferase M1 and its variants A and B as host factors of bladder cancer susceptibility: a case-control study. Cancer Res 54:4103–4111
Miners JO, Mackenzie PI (1991) Drug glucuronidation in humans. Pharmacol Ther 51:347–369
Owens IS, Ritter JK (1992) The novel bilirubin/phenol UDP-glucuronosyltransferase UGT1 gene locus: implications for multiple familial hyperbilirubinaemia phenotypes. Pharmacogenetics 2:93–108
Bosma PJ, Roy Chowdhury J, Huang T-J, Lahiri P, Oude Elferink RPJ, van Es HHG, Lederstein M, Whitington PF, Jansen PLM, Roy Chowdhury N (1992) Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients wiht Crigler-Najjar syndrome, type I. FASEB J 6:2859–2863
Ritter JK, Yeatman MT, Ferreira P, Owens IS (1992) Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patients. J Clin Invest 90:150–155
Bosma PJ, Roy Chowdhury N, Goldhoorn BG, Hofker MH, Oude Elferink RPJ, Jansen PLM, Roy Chowdhury J (1992) Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology 15:941–947
Moghrabi N, Clarke DJ, Burchell B, Boxer M (1993) Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syndrome type I: implication in carrier detection and prenatal diagnosis. Am J Hum Genet 53:722–729
Moghrabi N, Clarke DJ, Boxer M, Burchell B (1993) Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2. Genomics 18:171–173
Ritter JK, Yeatman MT, Kaiser C, Gridelli B, Owens IS (1993) A phenylalanine codon deletion at the UGT1 genecomplex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase. J Biol Chem 268:23573–23579
Erps LT, Ritter JK, Hersh JH, Blossom D, Martin NC, Owens IS (1994) Identification of 2 single-base substitutions in the UGT1 gene locus which abolish bilirubin uridine-diphosphate glucuronosyltransferase activity in vitro. J Clin Invest 93:564–570
Ciotti M, Yeatman MT, Sokol RJ, Owens IS (1995) Altered coding for a strictly conserved di-glycine in the major bilirubin UDP-glucuronosyltransferase of a Crigler-Najjar type I patient. J Biol Chem 270:3284–3291
Burchell B, Coughtrie MWH (1989) UDP-glucuronosyltransferases. Pharmacol Ther 43:261–289
de Morais SM, Uetrecht JP, Wells PG (1992) Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert's syndrome. Gastroenterology 102:577–586
Patel M, Tang BK, Kalow W (1992) Variability of acetaminophen metabolism in Caucasians and Orientals. Pharmacogenetics 2:38–45
Yue QY, Svensson JO, Sjoqvist F, Sawe J (1991) A comparison of the pharmacokinetics of codeine and its metabolites in healthy Chinese and Caucasian extensive hydroxylators of debrisoquine. Br J Clin Pharmacol 31:643–647
Liu HF, Vincent-Viry M, Galteau MM, Gueguen R, Magdalou J, Nicolas A, Leroy P, Siest G (1991) Urinary glucuronide excretion of fenofibric and clofibric acid glucuronides in man. Is it polymorphic? Eur J Clin Pharmacol 41:153–159
Vincent-Viry M, Cossy C, Galteau MM, Gueguen R, Magdalou J, Nicolas A, Leroy P, Siest G (1995) Lack of a genetic polymorphism in the glucuronidation of fenofibric acid. Pharmacogenetics 5:50–52
Weinshilboum R (1990) Sulphotransferase pharmacogenetics. Pharmacol Ther 45:93–107
Price RA, Cox NJ, Spielman RS, Van Loon JA, Maidak BL, Weinshilboum RM (1988) Inheritance of human platelet thermolabile phenol sulphotransferase (TLPST) activity. Genet Epidemiol 5:1–15
Price RA, Spielman RS, Lucena AL, Van Loon JA, Maidak BL, Weinshilboum RM (1989) Genetic polymorphism for human platelet thermostable phenol sulphotransferase (TSPST) activity. Genetics 122:905–914
Jones AL, Roberts RC, Coughtrie MWH (1993) The human phenolsulphotransferase polymorphism is determined by the level of expression of the enzyme protein. Biochem J 296:287–290
Ozawa S, Nagata K, Shimada M, Ueda M, Tsuzuki T, Yamazoe Y, Kalo R (1995) Primary strucutures and properties of two related forms of aryl sulfotransferases in human liver. Pharmacogenetics 5: S135-S140
Aksoy IA, Sochorova V, Weinshilboum RM (1993) Human liver dehydroepiandrosterone sulfotransferase: nature and extent of individual variation. Clin Pharmacol Ther 54:498–506
Otterness DM, Wieben ED, Wood TC, Watson RWG, Madden BJ, McCormick DJ, Weinshilboum RM (1992) Human liver dehydroepiandrosterone sulfotransferase: molecular cloning and expression of cDNA. Mol Pharmacol 41:865–872
Zhu X, Veronese ME, Bernard CCA, Sansom LN, McManus ME (1993) Identification of two human brain aryl sulfotransferase cDNAs. Biochem Biophys Res Commun 195:120–127
Wilborn TW, Comer KA, Dooley TP, Reardon IM, Heinrikson RL, Falany CN (1993) Sequence analysis and expression of the cDNA for the phenol sulfating form of human liver phenol sulfotransferase. Mol Pharmacol 43:70–77
Aksoy IA, Wood TC, Weinshilboum R (1994) Human liver estrogen sulfotransferase: identification by cDNA cloning and expression. Biochem Biophys Res Commun 200:1621–1629
Bernier F, Leblanc G, Labrie F, Luu-The V (1994) Structure of human estrogen and aryl sulfotransferase gene. J Biol Chem 269:28200–28205
Otterness DM, Her C, Aksoy S, Kimura S, Wieben ED, Weinshilboum RM (1995) Human dehydroepiandrosterone sulfotransferase gene: molecular cloning and structural characterization. DNA Cell Biol 14:331–341
Zhu X, Veronese ME, Sansom LN, McManus ME (1993) Molecular characerization of a human aryl sulfotransferase cDNA. Biochem Biophys Res Commun 192:671–676
Jones AL, Hagen M, Coughtrie MWH, Roberts RC, Glatt H (1995) Human platelet phenolsulfotransferases: cDNA cloning, stable expression in V79 cells and identification of a novel allelic variant of the phenol-sulfating form. Biochem Biophys Res Commun 208:855–862
Ganguly TC, Krasnykh V, Falany CN (1995) Xenobiotic sulfation by expressed human monoamine sulfating form of phenol sulfotransferase (hM-PST); comparison with phenol sulfating form of phenol sulfotransferase (hP-PST). FASEB J 9:A690
Romiti P, Giuliani L, Pacifici GM (1992) Interindividual variation in the N-sulphation of desipramine in human liver and platelets. Br J Clin Pharmacol 33:17–23
Weinshilboum R (1989) Methyltransferase pharmacogenetics. Pharmacol Ther 43:77–90
Weinshilboum R, Sladek SL (1980) Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 32:651–662
Krynetski EY, Schuetz JD, Galpin AJ, Pui C-H, Relling MV, Evans WE (1995) A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci USA 92:949–953
Lennard L (1992) The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 43:329–339
Lennard L, van Loon JA, Weilshilboum RM (1989) Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 46:149–154
Lennard L, Lilleyman JS, van Loon J, Weinshilboum RM (1990) Genetic variation in response to 6-mercaptopurine for childhood acute leukaemia. Lancet 236:225–229
Krynetski EY, Krynetski NF, Yanishevski Y, Evans WE (1995) Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase. Mol Pharmacol 47:1141–1147
Evans WE, Horner M, Chu YQ, Kalwinsky D, Roberts WM (1991) Altered mercaptopurine metabolism, toxic effects and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukaemia. J Pediatr 119:985–989
Hollander AAMJ, Vansaase JLCM, Kootte AMM, Vandorp WT, Vanbockel HJ, Vanes LA, Vanderwoude FJ (1995) Beneficial-effects of conversion from cyclosporine to azathioprine after kidney-transplantation. Lancet 345:610–614
Schutz E, Gummert J, Mohr F, Oellerich M (1993) Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 341:436–437
Hanioka N, Kimura S, Meyer UA, Gonzalez FJ (1990) The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934 to A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3′ splice recognition site. Am J Hum Genet 47:994–1001
Gough AC, Miles JS, Spurr NK, Moss JE, Gaedigk A, Eichelbaum M, Wolf CR (1990) Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature 347:773–776
Tyndale R, Aoyama T, Broly F, Matsunaga T, Inaba T, Kalow W, Gelboin HV, Meyer UA, Gonzalez FJ (1991) Identification of a new CYP2D6 allele lacking the codon encoding Lys-201: possible association with the poor metabolizer phenotype. Pharmacogenetics 1:26–32
Gaedigk A, Blum M, Gaedigk R, Eichelbaum M, Meyer UA (1991) Deletion of the entire cytochrome P450 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 48:943–950
Marez D, Sabbagh N, Legrand M, Lo-Guidice JM, Boone P, Broly F (1995) A novel CYP2D6 allele with an abolished splice recognition site associated with the poor metabolizer phenotype. Pharmacogenetics (in press)
Broly F, Marez D, Sabbagh N, Legrand M, Boone P, Meyer UA (1995) An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis. Pharmacogenetics, (in press)
Panserat S, Mura C, Gerard N, Vincent-Viry M, Galteau MM, Jacqz-Aigrain E, Krishnamorthy R (1994) DNA haplotypedependent differences in the amino acid sequence of debrisoquine 4-hydroxylase (CYP2D6): evidence for two major allozymes in extensive metabolisers. Hum Genet 94:401–406
Ingelman-Sundberg M, Oscarson M, Persson I, Masimirembwa CM, Dahl M-L, Bertilsson L, Sjoqvist F, Johansson I (1995) Genetic polymorphism of human drug metabolizing enzymes. Recent aspects on polymorphic forms of cytochromes P450. In: Boobis A (ed) COSTB1 meeting proceedings. Luxembourg: Office for Official Publications of the European Communities
Dahl ML, Johansson I, Bertilsson L, Ingelman-Sundberg M, Sjoqvist F (1995) Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. J Pharm Exp Ther 274:516–520
Evert B, Griese E-U, Eichelbaum M (1994) Cloning and sequencing of a new non-functional CYP2D6 allele: deletion of T1975 in exon 3 generates a premature stop codon. Pharmacogenetics 4:271–274
Daly AK, Leathart JBS, London SJ, Idle JR (1995) An inactive cytochrome P450 CYP2D6 allele containing a deletion and abase substitution. Human Genetics 95:337–341
Vatsis KP, Weber WW, Bell DA, Dupret J-M, Evans DAP, Grant DM, Hein DW, Lin HJ, Meyer UA, Relling MV, Sim E, Suzuki T, Yamazoe Y (1995) Nomenclature for N-acetyl-transferases. Pharmacogenetics 5:1–17
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Daly, A.K. Molecular basis of polymorphic drug metabolism. J Mol Med 73, 539–553 (1995). https://doi.org/10.1007/BF00195139
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00195139