Farmacogenetica: geneesmiddelentherapie aangepast aan het genotype van de patiënt?


onder medeverantwoordelijkheid van de redactiecommissie

Mutaties of polymorfismen in genen die coderen voor enzymen die van belang zijn bij de biotransformatie, het transport en de receptorbinding van geneesmiddelen, blijken frequent voor te komen in de populatie. Zij spelen mede een rol bij het risico van bijwerkingen in een individu of de kans op verminderde effectiviteit van een medicamenteuze therapie. De theorie en de (momenteel nog beperkte) praktische toepassingen komen in dit artikel aan de orde (Gebu 2003; 37: 25-30).

 






1. Sander C. Genomic medicine and the future of health care. Science 2000; 287: 1977-1978. 
2. Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet 2000; 356: 1667-1671. 
3. Kleyn P, Vesell ES. Genetic variation as a guide to drug development. Science 1998; 281: 1820-1821. 
4. Brookes AJ. The essence of SNPs. Gene 1999; 234: 177-186. 
5. Gibson GG, Skett P (eds.). Introduction to drug metabolism. Glasgow: Blackie Academic & Professional, 1994. 
6. Weide J van der, Steijns LSW. Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem 1999; 36: 722-729. 
7. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286: 487-491. 
8. Alvan G, Bechtel P, Iselius L, Gundert-Remy U. Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 1990; 39: 533-537. 
9. Andreassen OA, MacEwan T, Gulbrandsen AK, McCreadie RG, Steen VM. Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients. Psychopharmacology 1997; 131: 174-179. 
10. Schillevoort I, Boer A de, Weide J van der, Steijns LSW, Roos RAC, Jansen PAF, et al. Antipsychotic-induced extrapyrimidal syndromes and cytochrome P450-2D6 genotype: a case-control study. Pharmacogenetics 2002; 12: 235-240. 
11. Scordo MG, Spina E, Romeo P, Dahl ML, Bertilsson L, Johansson I, et al. CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients. Eur J Clin Pharmacol 2000; 56: 679-683. 
12. Armstrong M, Daly AK, Blennerhassett R, Ferrier N, Idle JR. Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype. Br J Psychiatry 1997; 170: 23-26. 
13. Lam LCW, Garcia-Barcelo MM, Ungvari GS, Tang WK, Lam VKL, Kwong SL, et al. Cytochrome P450 2D6 genotyping and association with tardive dyskinesia in Chinese schizophrenic patients. Pharmacopsychiatry 2001; 34: 238-241. 
14. Vries EM de, Pot HJ, Conemans JM, Uges DR. The clinical relevance of routine genotyping of CYP2D6/2C19 null alleles of psychiatric patients. Br J Clin Pharmacol 2002; 53: 550-551. 
15. Schillevoort I. Drug-induced extrapyramidal syndromes. Utrecht, Academisch proefschrift, 2002. 
16. Verstuyft C, Morin S, Robert A, Loriot MA, Beaune P, Jaillon P, et al. Early acenocoumarol overanticoagulation among cytochrome P450 2C9 poor metabolizers. Pharmacogenetics 2001; 11: 735-737. 
17. Hermida J, Zarza J, Alberca I, Montes R, Lopez ML, Molina E, et al. Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol. Blood 2002; 99: 4237-4239. 
18. Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics 2002; 12: 251-263. 
19. Thijssen H. Invloed van polymorfisme in cytochroom P450 enzymen op de gevoeligheid voor acenocoumerol. Tromnibus 2000; 28: 21-25. 
20. Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353: 717-719. 
21. Rogers JF, Nafziger AN, Bertino JS Jr. Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P 450-metabolized drugs. Am J Med 2002; 113: 746-750. 
22. Niemi M, Cascorbi I, Timm R, Kroemer HK, Neuvonen PJ, Kivisto KT. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther 2002; 72: 326-332. 
23. Schaeffeler E, Lang T, Zanger UM, Eichelbaum M, Schwab M. High-throughput genotyping of thiopurine S-methyltransferase by denaturing HPLC. Clin Chem 2001; 47: 548-555. 
24. McLeod HL, Krynetski EY, Relling MV, Evans WE. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 2000; 14: 567-572. 
25. Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 1999; 91: 2001-2008. 
26. Lennard L, Lilleyman JS. Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the thiopurine methyltransferase genetic polymorphism. Ther Drug Monit 1996; 18: 328-334. 
27. Arranz M, Munro J, Birkett J, Bolonna A, Mancama D, Sodhi M, et al. Pharmacogenetic prediction of clozapine respons. Lancet 2000; 355: 1615-1616. 
28. Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM, et al. The effect of polymorphisms of the r2-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med 2000; 162: 75-80. 
29. Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM, et al. Effect of polymorphism of the r2-adrenergic receptor on response to regular use of albuterol in asthma. Int Arch Allergy Immunol 2001; 124: 183-186. 
30. Palmer LJ, Silverman ES, Weiss ST, Drazen JM. Pharmacogenetics of asthma. Am J Respir Crit Care Med 2002; 165: 861-866. 
31. Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, et al. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet 1997; 349: 1353-1357. 
32. Psaty BM, Smith NL, Heckbert SR, Vos HL, Lemaitre RN, Reiner AP, et al. Diuretic therapy, the alpha-adducin gene variant, and the risk of myocardial infarction or stroke in persons with treated hypertension. JAMA 2002; 287: 1680-1689. 
33. Maitland-van der Zee AH, Klungel OH, Stricker BHC, Verschuren WM, Kastelein JP, Leufkens HGM, et al. Genetic polymorphisms: importance for response to HMG-CoA reductase inhibitors. Atherosclerosis 2002; 163: 213-222. 
34. Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-1457. 
35. Vandenbroucke JP, Meer FJ van der, Helmerhorst FM, Rosendaal FR. Factor V Leiden: should we screen oral contraceptive users and pregnant women? BMJ 1996; 313: 1127-1130. 
36. Veenstra DL, Higashi MK, Philips KA. Assessing the cost-effectiveness of pharmacogenomics. AAPS Pharmsci 2000; 2: E29. 
37. Gezondheidsraad. Farmacogenetica. Den Haag: Gezondheidsraad, 2000. Publicatienummer 2000/19. Zie ook: www.gr.nl.  

Auteurs

  • prof. dr A. de Boer, mw drs A.H. Maitland-van der Zee