Phenocopy and phenoconversion: Do they complicate association studies?

Pharmacogenomics

Volumn 13, Issue 9, 2012, Pages 981-984

  Shah, Rashmi R ^a   Smith, Robert L ^b  

^a Rashmi Shah Consultancy Ltd   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

drug interactions; fluoxetine; genotype; genotype phenotype mismatch; paroxetine; personalized medicine; pharmacogenetic association studies; pharmacogenetics; phenocopy; quinidine

Indexed keywords

6 MERCAPTOPURINE DERIVATIVE; AMFEBUTAMONE; AMIODARONE; CIMETIDINE; CINACALCET; CLOPIDOGREL; CODEINE; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; DEXTROMETHORPHAN; DIPHENHYDRAMINE; FLUINDOSTATIN; FLUOXETINE; IRINOTECAN; METHADONE; OMEPRAZOLE; PAROXETINE; PERPHENAZINE; QUINIDINE; SEROTONIN UPTAKE INHIBITOR; TAMOXIFEN; WARFARIN;

BLEEDING; BREAST CANCER; DIGESTIVE SYSTEM ULCER; DRUG EFFICACY; DRUG METABOLISM; DRUG POTENTIATION; DRUG RESPONSE; DRUG SAFETY; GENE CONVERSION; GENETIC ASSOCIATION; GENOTYPE; HEART ATRIUM FIBRILLATION; HOT FLUSH; HUMAN; PERSONALIZED MEDICINE; PHARMACOGENETICS; PHENOCONVERSION; PHENOCOPY; PHENOTYPE; REVIEW; UNSPECIFIED SIDE EFFECT;

BIOMARKERS, PHARMACOLOGICAL; GENETIC ASSOCIATION STUDIES; HUMANS; INDIVIDUALIZED MEDICINE; PHENOTYPE;

EID: 84864417886     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.12.71     Document Type: Review

References (26)

1. Brockmöller J, Kirchheiner J, Meisel C, Roots I. Pharmacogenetic diagnostics of cytochrome P450 polymorphisms in clinical drug development and in drug treatment. Pharmacogenomics 1(2), 125-151 (2000).
2. Kirchheiner J, Bertilsson L, Bruus H, Wolff A, Roots I, Bauer M. Individualized medicine-implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Pharmacopsychiatry 36(Suppl. 3), S235-S243 (2003).
3. 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 9(5), 442-473 (2004).
4. Brøsen K, Gram LF, Haghfelt T, Bertilsson L. Extensive metabolizers of debrisoquine become poor metabolizers during quinidine treatment. Pharmacol. Toxicol. 60(4), 312-314 (1987).
5. Ayesh R, Dawling S, Hayler A et al. Comparative effects of the diastereoisomers, quinine and quinidine in producing phenocopy debrisoquine poor metabolisers (PMs) in healthy volunteers. Chirality 3(1), 14-18 (1991).
6. Vormfelde SV, Brockmöller J, Bauer S et al. Relative impact of genotype and enzyme induction on the metabolic capacity of CYP2C9 in healthy volunteers. Clin. Pharmacol. Ther. 86(1), 54-61 (2009).
7. O'Neil WM, Gilfix BM, Markoglou N, Di Girolamo A, Tsoukas CM, Wainer IW. Genotype and phenotype of cytochrome P450 2D6 in human immunodeficiency virus-positive patients and patients with acquired immunodeficiency syndrome. Eur. J. Clin. Pharmacol. 56(3), 231-240 (2000).
8. Mitchell SC, Shah RR, Clements DG, Smith RL. Changes in debrisoquine hydroxylation capacity following liver surgery. Hum. Exp. Toxicol. 13(8), 537-541 (1994).
9. Monek O, Paintaud G, Bechtel Y, Miguet JP, Mantion G, Bechtel PR. Influence of donor and recipient genotypes on CYP2D6 phenotype after liver transplantation: a study of mutations CYP2D63 and CYP2D64. Eur. J. Clin. Pharmacol. 54(1), 47-52 (1998).
10. Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM. Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe. J. Clin. Pharmacol. 41(4), 443-451 (2001).
11. Nakashima D, Takama H, Ogasawara Y et al. Effect of cinacalcet hydrochloride, a new calcimimetic agent, on the pharmacokinetics of dextromethorphan: in vitro and clinical studies. J. Clin. Pharmacol. 47(10), 1311-1319 (2007).
12. Güzey C, Norström A, Spigset O. Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment with bupropion. Ther. Drug Monit. 24(3), 436-437 (2002).
13. Shiran MR, Chowdry J, Rostami-Hodjegan A et al. A discordance between cytochrome P450 2D6 genotype and phenotype in patients undergoing methadone maintenance treatment. Br. J. Clin. Pharmacol. 56(2), 220-224 (2003).
14. Ieiri I, Yamada S, Seto K et al. A CYP2D6 phenotype-genotype mismatch in Japanese psychiatric patients. Pharmacopsychiatry 36(5), 192-196 (2003).
15. Zourková A, Hadasová E. Paroxetine-induced conversion of cytochrome P450 2D6 phenotype and occurence of adverse effects. Gen. Physiol. Biophys. 22(1), 103-113 (2003).
16. Laine K, Tybring G, Härtter S et al. Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clin. Pharmacol. Ther. 70(4), 327-335 (2001).
17. Dalén P, Dahl M, Andersson K, Bertilsson L. Inhibition of debrisoquine hydroxylation with quinidine in subjects with three or more functional CYP2D6 genes. Br. J. Clin. Pharmacol. 49(2), 180-184 (2000).
18. Caraco Y, Sheller J, Wood AJ. Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects. J. Pharmacol. Exp. Ther. 290(1), 413-422 (1999).
19. Ito K, Brown HS, Houston JB. Database analyses for the prediction of in vivo drug-drug interactions from in vitro data. Br. J. Clin. Pharmacol. 57(4), 473-486 (2004).
20. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am. Fam. Physician 76(3), 391-396 (2007).
21. Kiyotani K, Mushiroda T, Hosono N et al. Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response. Pharmacogenet. Genomics 20(9), 565-568 (2010).
22. Kelly CM, Juurlink DN, Gomes T et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 340, C693 (2010).
23. Kreutz RP, Stanek EJ, Aubert R et al. Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study. Pharmacotherapy 30(8), 787-796 (2010).
24. Klein TE, Altman RB, Eriksson N et al.; for International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. N. Engl. J Med. 360(8), 753-764 (2009).
25. Lockhart P, Guthrie B. Trends in primary care antidepressant prescribing 1995-2007: a longitudinal population database analysis. Br. J. Gen. Pract. 61(590), E565-E572 (2011).
26. Preskorn SH, Shah R, Neff M, Golbeck AL, Choi J. The potential for clinically significant drug-drug interactions involving the CYP 2D6 system: effects with fluoxetine and paroxetine versus sertraline. J. Psychiatr. Pract. 13(1), 5-12 (2007).