Should thiopurine methyltransferase genotypes and phenotypes be measured before thiopurine therapy in patients with inflammatory bowel disease?

Therapeutic Drug Monitoring

Volumn 34, Issue 6, 2012, Pages 695-701

  Fangbin, Zhang ^a,b   Xiang, Gao ^b   Minhu, Chen ^b   Liang, Ding ^b   Feng, Xu ^a   Min, Huang ^b   Pinjin, Hu ^b  

^a THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIVERSITY   (China)

^b SUN YAT SEN UNIVERSITY   (China)

Author keywords

genotyping; inflammatory bowel disease; leucopenia; phenotyping; thiopurine; thiopurine methyltransferase

Indexed keywords

AZATHIOPRINE; MERCAPTOPURINE; MESALAZINE; PREDNISONE; THIOPURINE METHYLTRANSFERASE;

AGED; ARTICLE; BLOOD SAMPLING; CHINESE; CONTROLLED STUDY; COST EFFECTIVENESS ANALYSIS; CROHN DISEASE; DRUG INDICATION; FEMALE; FLU LIKE SYNDROME; FOLLOW UP; GENOTYPE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; LEUKOPENIA; LIVER TOXICITY; MAJOR CLINICAL STUDY; MALE; NEUTROPENIA; PANCREATITIS; PHENOTYPE; POLYMERASE CHAIN REACTION; PREDICTIVE VALUE; PRIORITY JOURNAL; REMISSION; SENSITIVITY AND SPECIFICITY; TREATMENT DURATION; ULCERATIVE COLITIS;

6-MERCAPTOPURINE; ADOLESCENT; ADULT; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; AZATHIOPRINE; CHINA; DRUG INTERACTIONS; DRUG MONITORING; FEMALE; FOLLOW-UP STUDIES; GENETIC ASSOCIATION STUDIES; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATORY BOWEL DISEASES; LEUKOPENIA; MALE; MESALAMINE; METHYLTRANSFERASES; MIDDLE AGED; MUTATION; PROSPECTIVE STUDIES; YOUNG ADULT;

EID: 84870039492     PISSN: 01634356     EISSN: 15363694     Source Type: Journal    
DOI: 10.1097/FTD.0b013e3182731925     Document Type: Article

References (30)

1. Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut. 2002;50: 485-489. (Pubitemid 34638866)
2. Ansari A, Arenas M, Greenfield SM, et al. Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Aliment Pharmacol Ther. 2008;28:973-983.
3. Hindorf U, Lindqvist M, Hildebrand H, et al. Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2006;24: 331-342. (Pubitemid 43972901)
4. Hindorf U, Lindqvist M, Peterson C, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006;55:1423-1431.
5. Krynetski EY, Krynetskaia NF, Yanishevski Y, et al. Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase. Mol Pharmacol. 1995;47:1141-1147.
6. Gardiner SJ, Gearry RB, Begg EJ, et al. Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clin Gastroenterol Hepatol. 2008;6:654-660.
7. Gisbert JP, Niño P, Rodrigo L, et al. Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-Term follow-up study of 394 patients. Am J Gastroenterol. 2006;101:2769-2776.
8. Sandborn WJ. Rational dosing of azathioprine and 6-mercaptopurine. Gut. 2001;48:591-592.
9. Gisbert JP, Luna M, Maté J, et al. Choice of azathioprine or 6-mercaptopurine dose based on thiopurine methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study. Hepatogastroenterology. 2006;53:399-404.
10. Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2-6. Discussion 16-19. (Pubitemid 20015811)
11. Zhang JP, Guan YY, Wu JH, et al. Phenotyping and genotyping study of thiopurine S-methyltransferase in healthy Chinese children: a comparison of Han and Yao ethnic groups. Br J Clin Pharmacol. 2004;58: 163-168.
12. Cao Q, Zhu Q, Shang Y, et al. Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease. Digestion. 2009;79:58-63.
13. Xin HW, Xiong H, Wu XC, et al. Relationships between thiopurine S-methyltransferase polymorphism and azathioprine-related adverse drug reactions in Chinese renal transplant recipients. Eur J Clin Pharmacol. 2009;65:249-255.
14. Zelinkova Z, Derijks LJ, Stokkers PC, et al. Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin Gastroenterol Hepatol. 2006;4:44-49.
15. Colombel JF, Ferrari N, Debuysere H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Cohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000; 118:1025-1030.
16. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet. 1980;32:651-662.
17. Schaeffeler E, Fischer C, Brockmeier D, et al. Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics. 2004;14:407-417.
18. Lennard L. TPMT in the treatment of Crohn's disease with azathioprine. Gut. 2002;51:143-146.
19. Krynetski EY, Evans WE. Genetic polymorphism of thiopurine S-methyltransferase: molecular mechanisms and clinical importance. Pharmacology. 2000;61:136-146.
20. Ansari A, Hassan C, Duley J, et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther. 2002;16:1743-1750.
21. Relling MV, Hancock ML, Rivera GK, et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst. 1999;91:2001-2008.
22. Lowry PW, Franklin CL, Weaver AL, et al. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut. 2001;49:656-664.
23. Woodson LC, Ames MM, Selassie CD, et al. Thiopurine methyltransferase. Aromatic thiol substrates and inhibition by benzoic acid derivatives. Mol Pharmacol. 1983;24:471-478.
24. Szumlanski CL, Weinshilboum RM. Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. Br J Clin Pharmacol. 1995;39: 456-459.
25. Lewis LD, Benin A, Szumlanski CL, et al. Olsalazine and 6-mercaptopurinerelated bone marrow suppression: a possible drug-drug interaction. Clin Pharmacol Ther. 1997;62:464-475.
26. Lowry PW, Szumlanski CL, Weinshilboum RM, et al. Balsalazide and azathiprine or 6-mercaptopurine: evidence for a potentially serious drug interaction. Gastroenterology. 1999;116:1505-1506.
27. Dewit O, Vanheuverzwyn R, Desager JP, et al. Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease. Aliment Pharmacol Ther. 2002;16:79-85.
28. Hande S, Wilson-Rich N, Bousvaros A, et al. 5-Aminosalicylate therapy is associated with higher 6-Thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine. Inflamm Bowel Dis. 2006;12:251-257.
29. de Graaf P, de Boer NK, Wong DR, et al. Influence of 5-Aminosalicylic acid on 6-Thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy. Br J Pharmacol. 2010;160:1083-1091
30. Shipkova M, Niedmann PD, Armstrong VW, et al. Determination of thiopurine methyltransferase activity in isolated human erythrocytes does not reflect putative in vivo enzyme inhibition by sulfasalazine. Clin Chem. 2004;50:438-441.