Pharmacogenomics as an Aspect of Molecular Autopsy for Forensic Pathology/Toxicology: Does Genotyping CYP 2D6 Serve as an Adjunct for Certifying Methadone Toxicity?

Journal of Forensic Sciences

Volumn 48, Issue 6, 2003, Pages 1406-1415

  Wong, Steven H ^a,b   Wagner, Michael A ^a,b   Jentzen, Jeffrey M ^a,b   Schur, Chuck ^b   Bjerke, Jeanette ^b   Gock, Susan B ^a,b   Chang, Chung Che ^b  

^a Milwaukee County Medical Examiner's Office   (United States)

^b MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

CYP 2D6; Forensic pathology; Forensic science; Forensic toxicology; Methadone toxicity; Molecular autopsy; Pharmacogenomics

Indexed keywords

CYTOCHROME P450 1A2; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; METHADONE;

ADULT; ALLELE; AUTOPSY; CLINICAL ARTICLE; CONFERENCE PAPER; DRUG METABOLISM; FEMALE; FORENSIC PATHOLOGY; GENOTYPE; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; MALE; PHARMACOGENOMICS; PRIORITY JOURNAL; RISK FACTOR;

EID: 0242526177     PISSN: 00221198     EISSN: None     Source Type: Journal    
DOI: 10.1520/jfs2002392     Document Type: Conference Paper

References (61)

1. Collins FS, Guttmacher AE. Genetics moves into the medical mainstream. JAMA 2001;286:2322-4.
2. Subramanian G, Adams MD, Venter JC, Broder S. Implications of the human genome for understanding human biology and medicine. JAMA 2001;286:2296-307.
3. Collins FS, McKusick V. Implication of the human genome project for medical science. JAMA 2001;280:540-4.
4. st century. JAMA 2001;286:2289-95.
5. Sadee W. Pharmacogenomics. BMJ 1999;319:1-4.
6. Sadee W. Implications of pharmacogenetics-pharmacogenomics - using genetic information to individualize drug therapy. Am Assoc Pharma Sci Newsletter 2001;4:18-23.
7. Linder MW, Prough RA, Valdes, Jr R. Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency. Clin Chem 1997;43:254-66.
8. Linder MW, Valdes R Jr. Fundamentals and applications of pharmacogenetics for the clinical laboratory. Ann Clin Lab Sci 1999;29:140-9.
9. Linder MW, Valdes R Jr. Pharmacogenetics in the practice of laboratory medicine. Molecular Diagnosis 1999;4:365-79.
10. Linder MW, Valdes R Jr. Genetic mechanisms for variability in drug response and toxicity. J Anal Tox 2001;25:405-13.
11. Wieczorek SJ, Tsongalis GJ. Pharmacogenomics: will it change the field of medicine? Clin Chim Acta 2001;308:1-8.
12. Wong SHY. Challenges of toxicology for the millennium. Ther Drug Monit 2000;22:52-7.
13. Schmitz G, Aslanidis C, Lackner KJ. Pharmacogenomics: implications for laboratory medicine. Clin Chim Acta 2001;308:43-53.
14. Steimer W, Muller B, Leucht S, Kissling W. Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy. Clin Chim Acta 2001;308:33-41.
15. Staples S. FDA okays visible genetics' HIV-resistance test. Genetic Eng News 2001;21(18):42.
16. Ingelman-Sundberg M, Daly AK, Oscarson M, Nebert DW. Human cytochrome P450 (CYP) genes: recommendations for the nomenclature of alleles. Pharmacogenetics 2000;10:91-3.
17. Ingelman-Sundberg M, Evans WE. Unravelling the functional genomics of the human CYP2D6 gene locus. Pharmacogenetics 2001;11:553-4.
18. Kirchheiner J, Brosen K, Dahl ML, Gram LF, Kasper S, Roots I, et al. CYP2D6 and CYP2C19 genotype-based dose recommendation for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand 2001;104:173-92.
19. Zanger UM, Fischer J, Raimundo S, Stuven T, Evert BO, Schwab M, et al. Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP2D6. Pharmacogenetics 2001;11:573-85.
20. Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 2001;2264-9.
21. Druid H, Holmgren P, Carlsson B, Ahlner J. Cytochorme P450 2D6(CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results. Forensic Sci Int 1999;99:25-34.
22. Chen S, Chou WH, Blouin RA, Mao Z, Humphries LL, Meek QC, et al. The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry. Clin Pharmacol Ther 1996;60:522-34.
23. Longenbach-Huber S, Safgren S, Raich T, George J, Ames MM, O'Kane DJ. Cytochrome P450(CYP450) genotyping on the Codelink™ Biorarray (Abstract). Clin Chem 2001;47:2085.
24. Lazarou J, Pomeranz B, Corey P. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279:1200-5.
25. Bates D, Cullen D, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse drug events and potential adverse drug events: implications for prevention. JAMA 1995;274:29-34.
26. Bates D, Gawande A. Error in medicine: what have we learned? Ann Intern Med 2000;132:763-7.
27. Johnson JA, Bootman JL. Drug-related morbidity and mortality. Arch Intern Med 1996;155:1949-56.
28. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA 2001;286:2270-9.
29. Litovitz TL, Klein-Schwartz W, White S, Cobaugh DJ, Youniss J, Omslaer JC, et al. 2000 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2001;19:337-95.
30. Caplehorn JRM, Drummer OH. Mortality associated with methadone programs. In: Spiehler V. Proceedings of the 1998 Joint SOFT/TIAFT International Meeting, Albuquerque, 1998;58-65.
31. Bell J, Bowron, Lewis J, Batey R. Serum levels of methadone in maintenance clients who persist in illicit drug use. Br J Addiction 1990;85:1599-602.
32. Kolar AF, Brown BS, Weddington WW, Ball JC. A treatment crisis: cocaine use by clients in methadone maintenance programs. J Substance Abuse Treatment 1990;7:101-7.
33. Karch SB. The pathology of drug abuse. Baco Raton: CRC, 1993;266-8.
34. Schur BC, Bjerke J, Nuwayhid N, Wong SH. Genotyping of cytochrome P450 2D6*3 and *4 mutations using conventional PCR. Clin Chim Acta 2001;308:25-31.
35. Wong SH, Bjerke J, Schur BC, Wagner MA, Chang J, Bratanow N. Optimization for genotyping CYP 2D6 by conventional and real-time PCR (Abstract). Clin Chem 2001;47:A77.
36. Schur BC, Bjerke J, Hubbard L, Wong SHY, Chang J, Nuwayhid N, et al. Genotyping CYP2D6 by conventional and real-time PCR (Abstract). J Anal Tox 2001;25:362.
37. Bon M, Vermes I, Van den Bergh FAJ, Neef C, Zijlstra E, Noorthoorn E, et al. Pharmacogenetics: a tool for therapeutic drug monitoring, a correlation study on CYP2D6 and nortriptyline (Abstract). Clin Chem 1998;44:A98.
38. Bjerke J, Chang C-C, Schur C, Wong S. Genotyping of cytochrome P450 2D6*4 mutation with fluorescent hybridization probes using LightCycler. In: Meuer S, Wittwer C, Nakagawara K, eds. Rapid cycle real-time PCR. Berlin: Springer, 2001;105-10.
39. Frank EL, Meadows CA, Lyon E. Detection of polymorphisms in the cytochrome P450 2D6 isoenzyme using real-time fluorescence PCR and melting curve analysis (Abstract). Clin Chem 2000;46(S6):A210-1.
40. Hersberger M, Marti-Jaun J, Rentsch K, Hanseller E. Rapid detection of the CYP2D6*3, CYP2D6*4 and CYP2D6*6 alleles by Tetra-Primer PCR and of the CYP2D6*5 allele by Multiplex Long PCR. Clin Chem 1999;46:1072-7.
41. Steimer W, Mueller B, Leucht S, Kisling W. Prevalence of cytochrome P450 2D6 (CYP2D6) and serotonin transporter (5HTT) polymorphisms in depressed inpatients compared to a control group (Abstract). Clin Chem 2000;46:A210.
42. Bjerke JM, Hubbard LJ, Wagner MA, Wong SHY. Genotyping CYP2D6*5 with long PCR and a designer proofreading enzyme that incorporates dUTP (Abstract). Ther Drug Monit 2001;23:492.
43. Manning T, Bidanset JH, Cohen S, Lukash L. Evaluation of the Abuscreen for Methadone. J Forensic Sci 1976;21:112-20
44. th ed. Foster City, CA: Chemical Toxicology Institute 1999;523-7.
45. Drug interactions. Micromedex Healthcare Seireds for Windows vol 107(database online). Greenwood Village, CO: Micromedex/Thomson Healthcare; 2001.
46. Wu D, Otton SV, Sproule BA, Busto U, Inaba T, Kalow W, et al. Inhibition of human cytochrome P450 2D6(CYP2D6) by methadone. Br J Clin Pharmacol 1993;35:30-4.
47. Eap CB, Bertschy G, Bauman P. High interindividual variability of methadone enantiomer blood levels to dose ratios. Arch Gen Pshcy 1998;55:89-90.
48. Iribarne C, Berthou F, Baird S, et al. Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol 1996;9:365-73.
49. Moody DE, Alburges ME, Parker RJ, Collins JM, Strong JM. The involvement of cytochrome P450 3A4 in N-demethylation of L-alpha-acetylmethadol(LAAM), norLAAM, and methadone. Drug Metab Disposit 1997;25:1347-53.
50. Topic E, Stefanovic M, Ivanisevic AM, Blazinic F, Culav J, Skocillic Z. CYP 2D6 genotyping in patients on psychoactive drug therapy. Clin Chem Lab Med 2000;38(9):921-7.
51. Raimundo S, Fischer J, Eichelbaum M, Griese E-U, Schwab M, Zanger UM. Elucidation of the genetic basis of the common "intermediate metabolizer" phenotype for drug oxidation by CYP2D6. Pharmacogenetics 2000;10:577-81.
52. Prouty RW, Anderson WH. The forensic science implications of site and temporal influences on postmortem blood-drug concentrations. J Forensic Sci 1990;35:243-70.
53. Anderson WH, Prouty RW. Postmortem redistribution of drugs. In: Baselt RC, editor. Advances in analytical toxicology. Chicago: Year Book Medical Publishers, Inc., 1989;70-102.
54. Fallini M. Contributo allo studio della circolazione ematica post-mortale. Minerva Medicolegale 1961;81:105-15.
55. Bertilsson L, Alm C, de la Carreras C, Edman G, Schalling D, Widen J. Debrisoquine hydroxylation polymorphism and personality. Lancet I 1989;555.
56. Llerena A, Edman G, Cobaleda J, Benitez J, Schalling D, Berilsson L. Relationship between personality and debrisoquine hydroxylation capacity. Suggestion of an endogenous neuroactive substrate or product of the cytochrome P450 2D6. Acta Psychiatr Scand 1992;14:261-4.
57. Swanson JR, Jone GR, Krasselt W, Denmark LN, Ratti F. Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms. J Forensic Sci 1997;42:335-9.
58. Van der Weide J, Steijins LSW, van Weelden MJM, de Haan K. The effect of genetic polymorphism of cytochrome P450 CYP 2C9 on phenytoin dose requirement. Pharmacogenetics 2001;11:287-91.
59. Odani A, Hashimoto Y, Otsuki Y, Uwai Y, Hatori H, Furusho K, et al. Genetic polymorphism of the CYP2C subfamily and its effect on the pharamcokinetics of phenytoin in Japanese patients with epilepsy. Clin Pharm Ther 1997;62:287-92.
60. Kosten TR, Gawin FH, Morgan C, Nelson JC, Jatlow P. Evidence for altered desipramine disposition in methadone-maintained patients treated for cocaine abuse. Am J Drug Alcohol Abuse 1990;16:329-36.
61. Maany I, Dhopesh V, Arndt IO, Burke W, Woody G, O'Brien CP. Increase in desipramine serum levels associated with methadone treatment. Am J Psychiat 1989;146:1611-3.