Non-tpmt determinants of azathioprine toxicity in inflammatory bowel disease

Annals of Gastroenterology

Volumn 23, Issue 2, 2010, Pages 95-101

  Katsanos, K ^a   Tsianos, E V ^a  

^a UNIVERSITY OF IOANNINA   (Greece)

Author keywords

Azathioprine; Efficacy; Inflammatory bowel disease; Non TPMT genes; Single nucleotide polymorphisms; Toxicity; TPMT

Indexed keywords

ALDEHYDE OXIDASE; AZATHIOPRINE; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; INOSINATE DEHYDROGENASE; INOSINE TRIPHOSPHATASE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MULTIDRUG RESISTANCE PROTEIN 1; PHOSPHATASE; RAC1 PROTEIN; THIOPURINE METHYLTRANSFERASE; TIOGUANINE; UNCLASSIFIED DRUG; XANTHINE DEHYDROGENASE; XANTHINE OXIDASE;

BACTERIAL INFECTION; BONE MARROW TOXICITY; DOSE RESPONSE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG MONITORING; DRUG WITHDRAWAL; ENTERITIS; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME DEGRADATION; FLU LIKE SYNDROME; GASTROINTESTINAL SYMPTOM; GENE LOCUS; GENE MUTATION; GENOTYPE; HUMAN; LEUKOPENIA; LIVER TOXICITY; LYMPHOMA; PANCREAS DISEASE; PHARMACOGENETICS; PREDICTION; PROTEIN FUNCTION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN ALLERGY;

EID: 77952938412     PISSN: 11087471     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (74)

1. Weinshiboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Gen 1980;32:651-652
2. Bokoch G. Regulation of innate immunity by Rho GTPases. Trends in Cell Biology 2005;15:163-171
3. Poppe D, Tiede I, Fritz G, Becker C, Bartsch B, Wirtz S, Strand D, Tanaka S, Galle PR, Bustelo XR, Neurath MF. Azathioprine suppresses ezrin-radixin-moesin-dependent T cel-APC coagulation through inhibition of Vav guanosisne exchange activity on Rac proteins. J Immunol 2006;176:641-651
4. Baker DE. Pharmacogenomics of azathioprine and 6-mer-captopurine in gastroenterologic therapy. Rev Gastroenterol Disord 2003; 3:150-157
5. Formea CM, Myers-Huentelman H, Wu R, Crabtree J, Fujita S, Hemming A, Reed A, Howard R, Karlix JL. Thiopurine S-methyltransferase genotype predicts azathioprine-in-duced myelotoxicity in kidney transplant recipients. Am J Transplant 2004;4:1810-1807
6. Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, Soule JC, Modigliani R, Touze Y, Catala P, Libersa C, Broly F. Genotypic analysis of thiopurine S-methyl-transferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000;118:1025-1030
7. Gearry RB, Barclay ML, Burt MJ, Collet JA, Chapman BA, Roberts RL, Kennedy MA. Thiopurine S-methyltransferase (TPMT) genotype does not predict adverse drug reactions to thiopurine drugs in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2003; 18:395-400
8. Sanderson J, Ansari A, Marinaki T, Duley J. Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy?Ann Clin Biochem 2004;41:294-302
9. Schwab M, Schaffeler E, Marx C, Fischer C, Lang T, Behrens C, Gregor M, Eichelbaum M, Zanger UM, Kaskas BA. Azathioprine ttherapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphisms. Pharmacogenetics 2002; 12:429-436
10. Connell WR, Kamm MA, Ritchie JK, Lennard-Jones JE. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience.Gut. 1993;34:1081-1085.
11. 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.
12. Present D, Meltzer SJ, Krumholz MP, Wolke A, Korelitz BI. 6-Mercaptopurine in the management of inflammatory bowel disease: short and long term toxicity. Ann Intern Med 1989;111:641-649.
13. Bouhnik Y, Lmann M, Mary JY, Scemama G, Tao R, Matuchansky C, Modigliani R, Rambaud JC. Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996;347:215-219.
14. Qasim A, Seery J, Buckley M, Morain CO. TPMT in the treatment of inflammatory bowel disease with azathioprine. Gut. 2003;52:767
15. Katsanos KH, Ferrante M, Henckaerts L, Joossens M, Schnitzler F, Arijs I, Van Assche G, Tsianos EV, Putgeerts P, Vermeire S. Bone marrow toxicity during azathioprine treatment in inflammatory bowel disease. Gut 2006;55(Suppl.V):A112
16. Pandya B, Thompson W, Poulton K, Bruce I, Payne D, Qasim F. Azathioprine toxicity and thiopurine methyltrans-ferase genotype in renal transplant patients. Transplant Proc 2002;34:1642-1645
17. Campell S, Ghosh S. Is neutropenia required for effective maintenance of remission during azathioprine therapy in inflammatory bowel disease. Eur J Gastroentrol Hepatol 2001;13:1073-1076
18. Regueiro M, Mardini H. Determining the thiopurine meth- yltransferase (TPMT) genotype minimizes the risk of acute myelosuppression and maximizes the initial dosing of azathioprine for the treatment of Crohn's disease. Gastroenterology 2001;120;3167
19. Evans WE. Pharmacogenetics of thiopurine S-methyltrans-ferase and thiopurine therapy. Ther Drug Monit 2004;26:186-191
20. Hon YY, Fessing MY, Pui C-H, Relling MV, Krynetski EY, Evans WE. Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Hum Mol Gen 1999;8:371-376
21. Ho GT, Lees C, Satsangi J. Pharmacogenetics and inflammatory bowel disease: progress and prospects. Inflamm Bowel Dis;10:148-158
22. McGovern DP, Travis SP. Thiopurine therapy: when to start and when to stop. Eur J Gastroentrol Hepatol 2003;15:219-223
23. Reuther LO, Vainer B, Sonne J, Larsen NE. Thiopurine meth-yltransferase (TPMT) genotype distribution in azathioprine tolerant and intolerant patients with various disorders. The impact of T-cell genotyping in predicting toxicity. Eur J Clin Pharmacol 2004;59:797-801
24. Arenas M, Simpson G, Lewis CM, Shobowale-Bakre el-M, Escuredo E, Fairbanks LD,Duley JA, Ansari A, Sanderson JD, Marinaki AM. Genetic variation in the MTHFR gene infuences thiopurine methyltransferase activity. Clin Chem 2005;51:2371-2374
25. Heckman JM, Lambson EM, Little F, Owen EP. Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events. J Neurol Sci 2005;231:71-80
26. Lennard L. TPMT in the treatment of Crohn's disease with azathioprine. Gut 2002; 51:143-146
27. Dubinski MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, Seidman EG. Pharmacogenomics and metabolite measurement for 6-mercaptopurine in inflammatory bowel disease. Gastroenterology 2000;118:705-713
28. van Dieren JM, van Vuuren AJ, Kusters JG, Nieuwenhuis EE, Kuipers EJ, van der Woude CJ. ITPA genotyping is not predictive for the development of side effects in AZA treated inflammatory bowel disease patients. Gut 2005;54:1664
29. Gisbert JP, Luna M, Mate J, Gonzalez-Guijarro L, Cara C, Pajares JM. Thiopurine methyltransferase activity and mye losuppressionin inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Medicina Clinica 2003;121:1-5
30. Cheung ST, Allan RN. Mistaken identity: misclassification of TPMT phenotype following blood transfusion. Eur J Gas-troentrol Hepatol 2003;15:1245-1247
31. Allorge D, Hamdan R, Broly F, Libersa C, Colombel JF. ITPA genotyping test does not improve detection of Crohn's disease patients at risk of azathioprine/6-mercaptopurine induced myelosuppresion. Gut 2005;54:565
32. Hindorf U, Lyrenas E, Nilsson A, Schmiegelow K. Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease. Scand J Gastroenterol 2004;39:1105-1112
33. Pettersson B, Almer S, Albertioni F, Soderhall S, Peterson C. Differences between children and adults in thiopurine methyltransferase activity and metabolite formation during thiopurine therapy: possible role of concomitant methotrexate. Ther Drg Monitor 2002;24:351-358
34. Derijks LJ, de Jong DJ, Gilissen LP, Engels LG, Hooymans PM, Jansen JB, Mulder CJ. 6-thioguanine seems promising in azathioprine-or 6-mercaptopurine-intolerant inflammatory bowel disease patients: a short term safety assessment. Eur J Gastroenterol Hepatol 2003;15;63-67
35. Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevancy. Clin Pharmacol Ther 2004;75:13-33
36. Brant SR, Panhuysen CI, Nicolae D, Reddy DM, Bonen DK, Karaliukas R, Zhang L, Swanson E, Datta LW, Moran T, Ravenhill G, Duerr RH, Achkar JP, Karban AS, Cho JH. MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet 2003;73:1282-1292
37. Katsanos KH, Ferrante M, Henckaerts L, Christodoulou D, Van Assche G, et al. Multidrug resistance (MDR) gene polymorphisms influence outcome of azathioprine and glucocorticoids in patients with inflammatory bowel disease. JCC 2007;1:2 (004)
38. Maeda T, Sumi S, Ueta A, Ohkubo Y, Ito T, Marinaki A, Kurono Y, Hasewawa S, Togari H. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population. Mol Genet Metabol 2005;85:271-279
39. Marsh S, King CR, Ahluwalia R, McLeod HL. Distribution of ITPA P32T alleles in multiple world populations. J Hum Genet 2004;49;579-581
40. Marinaki AM, Duley JA, Arenas M, Ansari A, Sumi S, Lewis CM, Shobowale-Bakre M, Fairbanks LD, Sanderson J. Mutation in the ITPA gene predicts intolerance to azathioprine. Nucleosides Nucleotides Nucleic Acids 2004;23:1393-1397
41. Zelinkova Z, Derijks LJ, Stokkers PC, Vogels EW,van Kampen AH, Curvers WL, Cohn D, van Deventer SJ, Hommes DW. Inosine triphosphate pyrophosphatase and thiopurine S-methyltransferase genotypes: relationship to azathioprine-induced myelosuppression. Clin Gastroenterol Hepatol 2006;4:44-49
42. von Ahsen N, Armstrong VW, Behrens C, von Tirpitz C, Stallmach A, Wang L, Weinshilboum R. Thiopurine S-meth- yltransferase pharmacogenetics: insights, challenges and future directions. Oncogene 2006;25:1629-1638.
43. De Ridder L, Van Dieren JM, Van Deventer HJ, Stokkers PC, Van der Woude JC, Van Vuuren AJ, Benninga MA, Escher JC, Hommes DW. Pharmacogenetics of thiopurine therapy in paediatric IBD patients. Aliment Pharmacol Ther. 2006;23:1137-1141.
44. Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees DC, Thein SL, Ansari A, Sanderson J, De Abreu RA, Simmonds HA, Duley JA. Genetic basis of inosine triphospshate pyrophosphohydrolase deficiency. Hum Gen 2002;111:360-367
45. Cao H, Hegele RA. DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. J Hum Genet 2002;47:620-622.
46. Gearry RB, Roberts RL, Barclay ML, Kennedy MA. Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine. Pharamacogenetics 2004;14:779-781
47. Matos P, Jordan P. Expression of Rac1b stimulates NF-?B- mediated cell survival and G1/S progression. Exp Cell Res 2005;305:292-299
48. Weed SA, Du Y, Parsons J. Thomas. Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1. J Cell Sci 1998;111:2433-2443
49. Nijhara R, van Hennik PB, Gignac ML, Kruhlak MJ, Hordijk PL, Delon J, Shaw S. Rac1 mediates collapse of microvilli on chemokine-activated T lympocytes. J Immunol 2004;173:4985-4993
50. Schnelzer A, Prechtel D, Knaus U, Dehne K, Gerhard M,Graeff H, Harbeck N, Schmitt M, Lengyel E. Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene 2000;19:3013-3020
51. Marinaki AM, Ansari A, Duley JA, Arenas M, Sumi S, Lewis CM, Shobowale-Bakre el-M, Escuredo E, Fairbanks LD, Sanderson JD. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics 2004;14:181-187
52. Yi P, Pogribny IP, James SJ. Multiplex PCR for simultaneous detection of 677C/T and 1298A/C polymorphisms in methylenetetrahydrofolate reductase gene for population studies of cancer risk. Cancer Lett 2002;181:209-213
53. Breen DP, Marinaki AM, Arenas M, Hayes PC. Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation. Liver Transpl. 2005;11:826-833
54. Clark M, Chow C-W, Rinaldo JE, Chalkley R. Correct usage of multiple transcription initiation sites and C/EBP-dependent transcription activation of the rat XDH/XO TATAless promoter requires down stream elements located on the coding region of the gene. Nucl Acids Res 1998;26:1801-1806.
55. Xu P, Zhu X, Huecksteadt TP, Brothman AR, Hoidal JR. Assignment of human xanthine dehydrogenase gene to chromosome 2p22.Genomics 1994;23:289-291
56. Albertini RJ. HPRT mutations in humans:biomarkers for mechanistic studies. Mutat Res 2001;489:1-16.
57. Horikawa K, Kawagucchi T, Ishihara S, Nagakura S, Hidaka M, Kagimoto T, Mitsuya H, Nakakuma H. Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients wirh paroxysmal nocturnal hemoglobinuria. Blood 2002;99:24-29
58. O'Neil JP, Finette BA. Transition mutations at CpG dinucleotides are the most frequent in vivo spontaneous singlebase substitution mutation in the human HPRT gene. Environ Molec Mut 1998;32:188-191.
59. Cariello NF, Craft TR, Vrieling H, van Zeeland AA, Adams T, Skopek TR. Human HPRT mutant database: software for data entry and retrieval. Environ Mol Mutagen 1992;20:81-83
60. Bowne S, Sullivan L, Blanton S, Cepko C, Blackshaw S, Birch D, Hughbanks-Wheaton D, Heckenlively JR, Daiger SP. Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa. Hum Molec Genet 2002;11:559-568
61. Siegel CA, Sands BE. Review article: practical management of inflammatory bowel disease patients taking immunomodulators.Aliment Pharmacol Ther. 2005;22:1-16.
62. Hande S, Wilson-Rich N, Bousvaros A, Zholudev A, Maurer R, Banks P, Makrauer F, Reddy S, Burakoff R, Friedman S. 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
63. Lewis LD, Benin A, Szumlanski CL, Otterness DM, Len nard L, Weinshilboum RM, Nierenberg DW. Olsalazine and 6-mercaptopurine related bone marrow suppression: a possi ble drug-drug interaction. Clin Pharmacol Ther 1997;62:464-475
64. Lowry PW, Franklin CL, Weaver AL, Szumlanski CL, Mays DC, Loftus EV, Tremaine WJLipsky JJ, Weinshilboum RM, Sandborn WJ. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut. 2001;49:656-664.
65. Biddal H, Helin P. Leucopenia in adult Still's disease during treatment with azathioprine and sulphasalazine. Clin Rheu matol 1987;6:244-250
66. Achkar JP, Brzezinski A, Lashner B, Vogel D, Seider D, Shen B. A double-blind, placebo-controlled randomized clinicall trial evaluating the effects of sulfasalazine on 6-mercaptopurine metabolism in patients with Crohn's disease. Am J Gastroenterol 2004;99;S264
67. Venkat Raman G, Sharman VL, Lee HA. Azathioprine and allopurinol: a potentially dangerous combination. J Intern Med 1990;228:69-71
68. Gossmann J, Kachel H, Schoeppe W, Scheuermann EH. Anemia in renal transplant receipients caused by concomit tant therapy with azathioprine and angiotensin-converting enzyme inhibitors. Tranplantation 1993;56:585
69. Roblin X, Serre-Debeauvais F, Phelip JM, Bessard G, Bonaz B. Drug interaction between infliximab and azathioprine in patients with Crohn's disease. Aliment Pharmacol Ther 2003;18:917-925
70. Bradley PP, Warden GD, Maxwell JG, Rothstein G. Neu tropenia and thrombocytopenia in renal allograft recipients treated with trimethoprim-sulfamethoxazole. Ann Intern Med 1980;93:560-562
71. Schaeffeler E, Eichelbaum M, Reinisch W, Zanger UM, Schwab M. Three novel thiopurine S-mthyltransferase allel ic variants (TPMT*20, *21, *22)-association with decreased enzyme function. Hum Mutat 2006;27:976.
72. Lysaa RA, Giverhaug T, Wold HL, Aarbakke J. Inhibition of human thiopurine methyltransferase by furosemide, ben droflumethiazide and trichloromethiazide. Eur J Clin Pharmacol 1996;49:393-396
73. Weinshilboum RM. Pharmacogenomics: catechol O-methyltransferase to thiopurine S-methyltransferase.Cell Mol Neurobiol. 2006;26:539-561.
74. Winter J, Walker A, Shapiro D, Gaffney D, Spooner RJ, Mills PR. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2004;20:593-599