Pharmacogenomic testing: Relevance in medical practice: Why drugs work in some patients but not in others

Cleveland Clinic Journal of Medicine

Volumn 78, Issue 4, 2011, Pages 243-257

  Kitzmiller, Joseph P ^a   Groen, David K ^a   Phelps, Mitch A ^b   Sadee, Wolfgang ^a  

^a THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOPIDOGREL; CYTOCHROME P450; DRUG DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PSYCHOTROPIC AGENT; TAMOXIFEN; TICLOPIDINE; WARFARIN;

GENETIC SCREENING; GENETICS; HUMAN; METHODOLOGY; PHARMACOGENETICS; REVIEW;

CYTOCHROME P-450 ENZYME SYSTEM; GENETIC TESTING; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; PHARMACOGENETICS; PSYCHOTROPIC DRUGS; TAMOXIFEN; TICLOPIDINE; WARFARIN;

EID: 79954514722     PISSN: 08911150     EISSN: None     Source Type: Journal    
DOI: 10.3949/ccjm.78a.10145     Document Type: Review

References (83)

1. King HC, Sinha AA. Gene expression profile analysis by DNA microarrays: promise and pitfalls. JAMA 2001; 286:2280-2288.
2. Nuckols TK, Paddock SM, Bower AG, et al. Costs of intravenous adverse drug events in academic and nonacademic intensive care units. Med Care 2008; 46:17-24.
3. Gurwitz JH, Field TS, Judge J, et al. The incidence of adverse events in two long-term care facilities. Am J Med 2005; 118:251-258.
4. Vargas E, Terleira A, Hernando F, et al. Effects of adverse drug reactions on length of stay in surgical intensive care units. Crit Care Med 2003; 31:694-698.
5. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279:1200-1205.
6. Field TS, Gilman BH, Subramanian S, Fuller JC, Bates DW, Gurwitz JH. The costs associated with adverse drug events in older adults in the ambulatory setting. Med Care 2005; 43:1171-1176.
7. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277:301-306.
8. Ernst FR, Grizzle AJ. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc (Wash) 2001; 41:192-199.
9. Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002; 3:229-243.
10. Sadee W. Measuring cis-acting regulatory variants genome-wide: new insights into expression genetics and disease susceptibility. Genome Med 2009; 1:116.
11. US Food and Drug Administration. Table of pharmacogenomic biomarkers in drug labels. http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm. Accessed 1/18/2011.
12. Budnitz DS, Shehab N, Kegler SR, Richards CL. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med 2007; 147:755-765.
13. Elias DJ, Topol EJ. Warfarin pharmacogenomics: a big step forward for individualized medicine: enlightened dosing of warfarin. Eur J Hum Genet 2008; 16:532-534.
14. Epstein RS, Moyer TP, Aubert RE, et al. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). J Am Coll Cardiol 2010; 55:2804-2812.
15. Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR. Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics 1994; 4:39-42.
16. Higashi MK, Veenstra DL, Kondo LM, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002; 287:1690-1698.
17. Sanderson S, Emery J, Higgins J. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. Genet Med 2005; 7:97-104.
18. Au N, Rettie AE. Pharmacogenomics of 4-hydroxycoumarin anticoagulants. Drug Metab Rev 2008; 40:355-375.
19. García-Martín E, Martínez C, Ladero JM, Agúndez JA. Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals. Mol Diagn Ther 2006; 10:29-40.
20. Sullivan-Klose TH, Ghanayem BI, Bell DA, et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996; 6:341-349.
21. Wen MS, Lee M, Chen JJ, et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes. Clin Pharmacol Ther 2008; 84:83-89.
22. Larramendy-Gozalo C, Yang JQ, Verstuyft C, et al. Genetic polymorphism of vitamin K epoxide reductase (VKORC1) 1173C>T in a Chinese and a Caucasian population. Basic Clin Pharmacol Toxicol 2006; 98:611-613.
23. Caldwell MD, Awad T, Johnson JA, et al. CYP4F2 genetic variant alters required warfarin dose. Blood 2008; 111:4106-4112.
24. Bristol-Myers Squibb. Coumadin (warfarin sodium) Prescribing Information. January 2010.
25. Barnes-Jewish Hospital at Washington University Medical Center. Warfarin dosing. http://warfarindosing.org Accessed 1/20/2011.
26. Flockhart DA, O'Kane D, Williams MS, et al. Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genet Med 2008; 10:139-150.
27. National Institutes of Health. ClinicalTrials.gov. http://clinicaltrials.gov. Accessed January 20, 2011.
28. Eckman MH, Rosand J, Greenberg SM, Gage BF. Cost-effectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation. Ann Intern Med 2009; 150:73-83.
29. Meckley LM, Gudgeon JM, Anderson JL, Williams MS, Veenstra DL. A policy model to evaluate the benefits, risks, and costs of warfarin pharmacogenomic testing. Pharmacoeconomics 2010; 28:61-74.
30. Patrick AR, Avron J, Choudhry NK. Cost-effectiveness of genotypeguided warfarin dosing for patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2009; 2:429-436.
31. Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis 2008; 25:52-60.
32. Bhatt DL. Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit? JAMA 2009; 302:896-897.
33. Shuldiner AR, O'Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009; 302:849-857.
34. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2009; 373:309-317.
35. Simon T, Verstuyft C, Mary-Krause M, et al. French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009; 360:363-375.
36. Paré G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010; 363:1704-1714.
37. Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Plavix (clopidogrel bisulfate) prescribing information. August 2010.
38. 450P Drug Interaction Table. Indiana University School of Medicine. http://medicine.iupui.edu/clinpharm/ddis/table.asp. Accessed 1/21/2011.
39. Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Writing Committee Members, Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O'Gara PT, Stein CM. ACCF/AHA clopidogrel clinical alert: approaches to the FDA "boxed warning" : a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation 2010; 122:537-557.
40. National Institutes of Health. Genotype Guided Comparison of Clopidogrel and Prasugrel Outcomes Study. http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00995514. Accessed 1/20/2011.
41. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: Review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009; 8:453-463.
42. SEARCH Collaborative Group, Link E, Parish S, Armitage J, et al. SLCO1B1 variants and statin-induced myopathy-a genomewide study. N Engl J Med 2008; 359:789-799.
43. Romaine SP, Bailey KM, Hall AS, Balmforth AJ. The influence of SLC01B1 (OATP1B1) gene polymorphisms on response to statin therapy. Pharmacogenomics J 2010; 10:1-11.
44. Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J 2010; Apr 13 [Epub ahead of print].
45. Goetz MP, Rae JM, Suman VJ, et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 2005; 23:9312-9318.
46. Beverage JN, Sissung TM, Sion AM, Danesi R, Figg WD. CYP2D6 polymorphisms and the impact on tamoxifen therapy. J Pharm Sci 2007; 96:2224-2231.
47. Flockhart D. CYP2D6 genotyping and the pharmacogenetics of tamoxifen. Clin Adv Hematol Oncol 2008; 6:493-494.
48. Goetz MP, Kamal A, Ames MM. Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther 2008; 83:160-166.
49. Stearns V, Rae JM. Pharmacogenetics and breast cancer endocrine therapy: CYP2D6 as a predictive factor for tamoxifen metabolism and drug response? Expert Rev Mol Med 2008; 10:e34.
50. Dezentjé VO, Guchelaar HJ, Nortier JW, van del Velde CJ, Gelderblom H. Clinical implications of CYP2D6 genotyping in tamoxifen treatment for breast cancer. Clin Cancer Res 2009; 15:15-21.
51. Higgins MJ, Rae JM, Flockhart DA, Hayes DF, Stearns V. Pharmacogenetics of tamoxifen: who should undergo CYP2D6 genetic testing? J Natl Compr Canc Netw 2009; 7:203-213.
52. Hoskins JM, Carey LA, McLeod HL. CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat Rev Cancer 2009; 9:576-586.
53. Steimer W, Zöpf K, von Amelunxen S, et al. Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clinical Cancer 2004; 50:1623-1633.
54. Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharm Ther 2008; 83:234-242.
55. Kirchheiner J, Nickchen K, Bauer M, et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004; 9:442-473.
56. Kirchheiner J, Schmidt H, Tzvetkov M, et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 2007; 7:257-265.
57. Kirchheiner J. CYP2D6 phenotype prediction from genotype: which system is the best? Clin Pharmacol Ther 2008; 83:225-227.
58. Borges S, Desta Z, Jin Y, et al. Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patients. J Clin Pharmacol 2010; 50:450-458.
59. Hoffmann-La Roche Ltd. AmpliChip CYP450 Test. http://www.roche.com/assays/Pages/AmpliChipCYP450Test.aspx. Accessed 1/21/2011.
60. Anzenbacher P, Anzenbacherová E. Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci 2001; 58:737-747.
61. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 2006; 368:704.
62. Willmann S, Edginton AN, Coboeken K, Ahr G, Lippert J. Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study. Clin Pharm Ther 2009; 86:634-643.
63. Grzesiak M, Beszłej A, Lebioda A, Jonkisz A, Dobosz T, Kienja A. [Retrospective assessment of the antidepressants tolerance in the group of patients with diagnosis of depression and different CYP2D6 genotype.] [In Polish] Psychiatr Pol 2003; 37:433-444.
64. Laika B, Leucht S, Heres S, Steimer W. Intermediate metabolizer: increased side effects in psychoactive drug therapy. The key to cost-effectiveness of pretreatment CYP2D6 screening? Pharmacogenomics J 2009; 9:395-403.
65. Rau T, Wohlleben G, Wuttke H, et al. CYP2D6 genotype: Impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study. Clin Pharm Ther 2004; 75:386-393.
66. McAlpine DE, O'Kane DJ, Black JL, Mrazek DA. Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clin Proc 2007; 82:1065-1068.
67. Chen S, Chou WH, Blouin RA, et al. The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry. Clin Pharmacol Ther 1996; 60:522-534.
68. Shams ME, Arneth B, Hiemke C, et al. CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther 2006; 31:493-502.
69. Whyte EM, Romkes M, Mulsant BH, et al. CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. Int J Geriatr Psychiatry 2006; 21:542-549.
70. Roberts RL, Mulder RT, Joyce PR, Luty SE, Kennedy MA. No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline. Hum Psychopharmacol 2004; 19:17-23.
71. Murphy GM Jr, Kremer C, Rodrigues HE, Schatzberg AF. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 2003; 160:1830-1835.
72. Gillman PK. Re: no evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline. Hum Psychopharmacol 2005; 20:61-62.
73. Gex-Fabry M, Eap CB, Oneda B, et al. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit 2008; 30:474-482.
74. Kawanishi C, Lundgren S, Agren H, Bertilsson L. Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study. Eur J Clin Pharmacol 2004; 59:803-807.
75. Serretti A, Calati R, Massat I, et al. Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with response and remission in a sample of depressive patients. Int Clin Psychopharmacol 2009; 24:250-256.
76. de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics 2006; 47:75-85.
77. de Leon J, Susce MT, Johnson M, et al. DNA microarray technology in the clinical environment: the AmpliChip CYP450 test for CYP2D6 and CYP2C19 genotyping. CNS Spectr 2009; 14:19-34.
78. Thuerauf N, Lunkenheimer J. The impact of the CYP2D6-polymorphism on dose recommendations for current antidepressants. Eur Arch Psychiatry Clin Neurosci 2006; 256:287-293.
79. Horstmann S, Binder EB. Pharmacogenomics of antidepressant drugs. Pharmacol Ther 2009; 124:57-73.
80. Ferreira Ade A, Neves FS, da Rocha FF, et al. The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder. J Affect Disord 2009; 112:267-272.
81. Serretti A, Kato M, De Ronchi D, Kinoshita T. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Mol Psychiatry 2007; 12:247-257.
82. Kato M, Serretti A. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry 2010; 15:473-500.
83. Reynolds GP, Zhang Z, Zhang X. Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapineinduced weight gain. Am J Psychiatry 2003; 160:677-679.