Genetic basis of drug metabolism

American Journal of Health-System Pharmacy

Volumn 59, Issue 21, 2002, Pages 2061-2069

  Ma, Margaret K ^a   Woo, Michael H ^a   McLeod, Howard L ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Antiinflammatory agents; Antituberculars; Hydralazine; Hypotensive agents; Isoniazid; Metabolism; Pharmacogenetics; Polymorphism; Race; Sulfonamides; Toxicity

Indexed keywords

ACYLTRANSFERASE; ANTIARRHYTHMIC AGENT; ANTIDEPRESSANT AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A; CYTOCHROME P450 ISOENZYME; DIAZEPAM; GLIPIZIDE; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; HYDRALAZINE; ISONIAZID; LOSARTAN; MEPHENYTOIN; MORPHINE DERIVATIVE; NEUROLEPTIC AGENT; NITROFURAN DERIVATIVE; NONSTEROID ANTIINFLAMMATORY AGENT; OMEPRAZOLE; PHENYTOIN; PRIMAQUINE; PROCAINAMIDE; SULFONAMIDE; SULFONE DERIVATIVE; TOLBUTAMIDE; UNINDEXED DRUG; VITAMIN K GROUP; WARFARIN;

ALLELE; ASIAN; BLEEDING; CAUCASIAN; DNA SEQUENCE; DRUG CLEARANCE; DRUG DISPOSITION; DRUG INDUCED CANCER; DRUG INDUCED DISEASE; DRUG METABOLISM; DRUG RESPONSE; ENZYME ACTIVITY; ETHNIC DIFFERENCE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HEMOLYTIC ANEMIA; HUMAN; HYPOGLYCEMIA; MULTIGENE FAMILY; NEGRO; PHARMACOGENETICS; PHARMACOGENOMICS; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT FAILURE;

EID: 0036830117     PISSN: 10792082     EISSN: None     Source Type: Journal    
DOI: 10.1093/ajhp/59.21.2061     Document Type: Review

References (93)

1. Vogel F. [Modern problems in genetics.] Ergeb Inn Med Kinderheilkd. 1959; 12:52-125. In German.
2. Phillips KA, Veenstra DL, Oren E et al. Potential role of pharmacogenomics in reducing adverse drug reactions: A systematic review. JAMA. 2001; 286:2270-9.
3. Evans DA, McLeod HL, Pritchard S et al. Interethnic variability in human drug responses. Drug Metab Dispos. 2001; 29:606-10.
4. Kalow W, Otton SV, Kadar D et al. Ethnic difference in drug metabolism: Debrisoquine 4-hydroxylation in Caucasians and Orientals. Can J Physiol Pharmacol. 1980; 58:1142-4.
5. Wood AJ. Ethnic differences in drug disposition and response. Ther Drug Monit. 1998; 20:525-6.
6. Daly AK, Brockmoller J, Broly F et al. Nomenclature for human CYP2D6 alleles. Pharmacogenetics. 1996; 6:193-201.
7. Kletzien RF, Harris PK, Foellmi LA et al. Glucose-6-phosphate dehydrogenase: A "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. FASEB J. 1994; 8:174-81.
8. Beutler E. G6PD deficiency. Blood. 1994; 84:3613-36.
9. Vulliamy TJ, D'Urso M, Battistuzzi G et al. Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia. Proc Natl Acad Sci. 1988; 85:5171-5.
10. Beutler E. The molecular biology of G6PD variants and other red cell enzyme defects. Annu Rev Med. 1992; 43:47-59.
11. Vulliamy T, Mason P, Luzzatto L et al. The molecular basis of glucose-6-phosphate dehydrogenase deficiency. Trends Genet. 1992; 8:138-43.
12. Carson PE, Ajmar F, Hashimoto F et al. Electrophoretic demonstration of stromal effects on haemolysate glucose-6-phosphate dehydrogenase and 6-phosphogluconic dehydrogenase. Nature. 1966; 210:813-5.
13. Hirono A, Beutler E. Molecular cloning and nucleotide sequence of cDNA for human glucose-6-phosphate dehydrogenase variant A(-). Proc Natl Acad Sci. 1988; 85: 3951-4.
14. Stroncek D, Procter JL, Johnson J. Drug-induced hemolysis: Cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction. Am J Hematol. 2000; 64:67-70.
15. Evans DA, Manley KA, McKusch VA et al. Genetic control of isoniazid metabolism in man. Br Med J. 1960; 2:485-91.
16. Evans DA. N-acetyltransferase. Pharmacol Ther. 1989; 42:157-234.
17. Wolkenstein P, Carriere V, Charue D et al. A slow acetylator genotype is a risk factor for sulphonamide-induced toxic epidermal necrolysis and Stevens-Johnson syndrome. Pharmacogenetics. 1995; 5:255-8.
18. Vatsis KP, Weber WW, Bell DA et al. Nomenclature for N-acetyltransferases. Pharmacogenetics. 1995; 5:1-17.
19. Knight RA, Selin MJ, Harris HW et al. Genetic factors influencing isoniazid blood levels in humans. Trans Conf Chemother Tuberc. 1959; 8:52-6.
20. Evans DA. Survey of human acetylator polymorphism in spontaneous disorders. J Med Genet. 1984; 21:243-53.
21. Nakagawa H, Sunahara S. [Studies on metabolism of isoniazid by a new chemical determination of isoniazid (the 2nd report). Trimodal distribution of blood levels, inactivation in intestine and combination of isoniazid with serum protein.] Kekkaku. 1967; 42:203-12. In Japanese.
22. Sunahara S, Motoyuki U, Ogawa M et al. Genetical and geographical studies on isoniazid inactivation. Science. 1961; 134: 1530-3.
23. Karim AK, Elfellah MS, Evans DA et al. Human acetylator polymorphism: Estimate of allele frequency in Libya and details of global distribution. J Med Genet. 1981; 18:325-30.
24. Cascorbi I, Drakoulis N, Brockmoller J et al. Arylamine N-acetyltransferase (NAT2) mutations and their allelic aflelic linkage in unrelated Caucasian individuals: Correlation with phenotypic activity. Am J Hum Genet. 1995; 57:581-92.
25. Cascorbi I, Brockmoller J, Bauer S et al. NAT2&12A (803A->G) codes for rapid arylamine N-acetylation in humans. Pharmacogenetics. 1996; 6:257-9.
26. Lin HJ, Han CY, Lin BK et al. Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics. 1994; 4:125-34.
27. Hein DW, Ferguson RJ, Doll MA et al. Molecular genetics of human polymorphic N-acetyltransferase: Enzymatic analysis of 15 recombinant wild-type, mutant, and chimeric NAT2 allozymes. Hum Mol Genet. 1994; 3:729-34.
28. Grant DM, Goodfellow GH, Sugamori K et al. Pharmacogenetics of the human arylamine N-acetyltransferases. Pharmacology. 2000; 61:204-11.
29. Kita T, Tanigawara Y, Chikazawa S et al. N-acetyltransferase2 genotype correlated with isoniazid acetylation in Japanese tuberculous patients. Biol Pharm Bull. 2001; 24:544-9.
30. Nelson DR, Koymans L, Kamataki T et al. P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 1996; 6:1-42.
31. Ingelman-Sundberg M, Oscarson M, Daly AK et al. Human cytochrome P-450 (CYP) genes: A web page for the nomenclature of alleles. Cancer Epidemiol Biomarkers Prev. 2001; 10:1307-8.
32. Ingelman-Sundberg M, Daly AK, Oscarson M et al. Human cytochrome P450 (CYP) genes: Recommendations for the nomenclature of alleles. Pharmacogenetics. 2000; 10:91-3.
33. Mahgoub A, Idle JR, Dring LG et al. Polymorphic hydroxylation of debrisoquine in man. Lancet. 1977; 2:584-6.
34. Ingelman-Sundberg M, Evans WE. Unravelling the functional genomics of the human CYP2D6 gene locus. Pharmacogenetics. 2001; 11:553-4.
35. Johansson I, Oscarson M, Yue QY et al. 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: 452-9.
36. Kagimoto M, Heim M, Kagimoto K et al. Multiple mutations of the human cytochrome P4502D6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. J Biol Chem. 1990; 265:17209-14.
37. Kroemer HK, Eichelbaum M. "It's the genes, stupid." Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. Life Sci. 1995; 56:2285-98.
38. Bertilsson L, Dahl ML, Sjoqvist F et al. Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet. 1993; 341:63. Letter.
39. Gaedigk A, Gotschall RR, Forbes NS et al. Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics. 1999; 9: 669-82.
40. Hanioka N, Kimura S, Meyer UA et al. The human CYP2D locus associated with a common genetic defect in drug oxidation: A G1934 - A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3′ splice recognition site. Am J Hum Genet. 1990; 47:994-1001.
41. Gaedigk A, Blum M, Gaedigk R et al. Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet. 1991; 48:943-50.
42. 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; 53:410-8.
43. Hamelin BA, Turgeon J, Vallee F et al. The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin Pharmacol Ther. 1996; 60:512-21.
44. Carrillo JA, Dahl ML, Svensson JO et al. Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. Clin Pharmacol Ther. 1996; 60:183-90.
45. Spina E, Gitto C, Avenoso A et al. Relationship between plasma desipramine levels, CYP2D6 phenotype and clinical response to desipramine: A prospective study. Eur J Clin Pharmacol. 1997; 51: 395-8.
46. Lledo P, Abrams SM, Johnston A et al. Influence of debrisoquine hydroxylation phenotype on the pharmacokinetics of mexiletine. Eur J Clin Pharmacol. 1993; 44:63-7.
47. Gross AS, Phillips AC, Rieutord A et al. The influence of the sparteine/debrisoquine genetic polymorphism on the disposition of dexfenfluramine. Br J Clin Pharmacol. 1996; 41:311-7.
48. Botsch S, Heinkele G, Meese CO et al. Rapid determination of CYP2D6 phenotype during propafenone therapy by analysing urinary excretion of propafenone glucuronides. Eur J Clin Pharmacol. 1994; 46: 133-5.
49. Kirchheiner J, Brosen K, Dahl ML et al. CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: A first step towards subpopulation-specific dosages. Acta Psychiatr Scand. 2001; 104:173-92.
50. Steward DJ, Haining RL, Henne KR et al. Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics. 1997; 7:361-7.
51. Bhasker CR, Miners JO, Coulter S et al. Allelic and functional variability of cytochrome P4502C9. Pharmacogenetics. 1997; 7:51-8.
52. Sullivan-Klose TH, Ghanayem BI, Bell DA et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics. 1996; 6:341-9.
53. Stubbins MJ, Harries LW, Smith G et al. Genetic analysis of the human cytochrome P450 CYP2C9 locus. Pharmacogenetics. 1996; 6:429-39.
54. Haining RL, Hunter AP, Veronese ME et al. Allelic variants of human cytochrome P450 2C9: Baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Arch Biochem Biophys. 1996; 333:447-58.
55. Rettie AE, Korzekwa KR, Kunze KL et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: A role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol. 1992; 5:54-9.
56. Higashi MK, Veenstra DL, Kondo LM et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA. 2002; 287:1690-8.
57. Ninomiya H, Mamiya K, Matsuo S et al. Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Ther Drug Monit. 2000; 22:230-2.
58. Aithal GP, Day CP, Kesteven PJ et al. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet. 1999; 353:717-9.
59. Tang C, Shou M, Rushmore TH et al. Invitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: Correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics. 2001; 11: 223-35.
60. Evans WE, Relling MV. Pharmacogenomics: Translating functional genomics into rational therapeutics. Science. 1999; 286:487-91.
61. Lasker JM, Wester MR, Aramsombatdee E et al. Characterization of CYP2C19 and CYP2C9 from human liver: Respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys. 1998; 353: 16-28.
62. Ibeanu GC, Goldstein JA, Meyer U et al. Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998; 286:1490-5.
63. Goldstein JA, de Morais SM. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics. 1994; 4:285-99.
64. De Morais SM, Wilkinson GR, Blaisdell J et al. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994; 269:15419-22.
65. Wilkinson GR, Guengerich FP, Branch RA et al. Genetic polymorphism of S-mephenytoin hydroxylation. Pharmacol Ther. 1989; 43:53-76.
66. 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.
67. Furuta T, Ohashi K, Kosuge K et al. CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther. 1999; 65:552-61.
68. Balian JD, Sukhova N, Harris JW et al. The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: a population study. Clin Pharmacol Ther. 1995; 57:662-9.
69. Furuta T, Ohashi K, Kamata T et al. Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer. Ann Intern Med. 1998; 129:1027-30.
70. Funck-Brentano C, Becquemont L, Lenevu A et al. Inhibition by omeprazole of proguanil metabolism: Mechanism of the interaction in vitro and prediction of in vivo results from the in vitro experiments. J Pharmacol Exp Ther. 1997; 280: 730-8.
71. Wan J, Xia H, He N et al. The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype. Br J Clin Pharmacol. 1996; 42: 471-4.
72. Qin XP, Xie HG, Wang W et al. Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects. Clin Pharmacol Ther. 1999; 66:642-6.
73. Cholerton S, Daly AK, Idle JR et al. The role of individual human cytochromes P450 in drug metabolism and clinical response. Trends Pharmacol Sci. 1992; 13: 434-9.
74. Shimada T, Yamazaki H, Mimura M et al. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther. 1994; 270: 414-23.
75. Paine MF, Shen DD, Kunze KL et al. Firstpass metabolism of midazolam by the human intestine. Clin Pharmacol Ther. 1996; 60:14-24.
76. Watkins PB. Cyclosporine and liver transplantation: Will the midazolam test make blood level monitoring obsolete? Hepatology. 1995; 22:994-6.
77. Schuetz JD, Beach DL, Guzelian PS et al. Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics. 1994; 4: 11-20.
78. Kolars JC, Lown KS, Schmiedlin-Ren P et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics. 1994; 4: 247-59.
79. Felix CA, Walker AH, Lange BJ et al. Association of CYP3A4 genotype with treatment-related leukemia. Proc Natl Acad Sci. 1998; 95:13176-81.
80. Rebbeck TR, Jaffe JM, Walker AH et al. Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst. 1998; 90: 1225-9.
81. Ball SE, Scatina J, Kao J et al. Population distribution and effects on drug metabolism of a genetic variant in the 5′ promoter region of CYP3A4. Clin Pharmacol Ther. 1999; 66:288-94.
82. Paris PL, Kupelian PA, Hall JM et al. Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients. Cancer Epidemiol Biomarkers Prev. 1999; 8:901-5.
83. Tayeb MT, Clark C, Ameyaw MM et al. CYP3A4 promoter variant in Saudi, Ghanaian and Scottish Caucasian populations. Pharmacogenetics. 2000; 10:753-6.
84. Wrighton SA, Brian WR, Sari MA et al. Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol Pharmacol. 1990; 38:207-13.
85. Wrighton SA, Ring BJ, Watkins PB et al. Identification of a polymorphically expressed member of the human cytochrome P-450III family. Mol Pharmacol. 1989; 36:97-105.
86. Kuehl P, Zhang J, Lin Y et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet. 2001; 27:383-91.
87. Dussault I, Lin M, Hollister K et al. Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem. 2001; 276:33309-12.
88. Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med. 2001; 7:584-90.
89. Xie W, Barwick JL, Downes M et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature. 2000; 406:435-9.
90. Forman BM. Polymorphisms in promiscuous PXR: An explanation for interindividual differences in drug clearance? Pharmacogenetics. 2001; 11:551-2.
91. Xie W, Barwick JL, Simon CM et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev. 2000; 14:3014-23.
92. McLeod HL. Pharmacogenetics: More than skin deep. Nat Genet. 2001; 29:247-8.
93. McLeod HL. Race and responsiveness to drugs for heart failure. N Engl J Med. 2001; 345:766-7.