Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?

World Journal of Gastroenterology

Volumn 20, Issue 13, 2014, Pages 3534-3541

  Stocco, Gabriele ^a   Pelin, Marco ^a   Franca, Raffaella ^b   De Iudicibus, Sara ^b   Cuzzoni, Eva ^a   Favretto, Diego ^b   Martelossi, Stefano ^b   Ventura, Alessandro ^a,b   Decorti, Giuliana ^a  

^a UNIVERSITY OF TRIESTE   (Italy)

^b INSTITUTE FOR MATERNAL AND CHILD HEALTH IRCCS BURLO GAROFOLO   (Italy)

Author keywords

Azathioprine; Glutathione S transferase; Inflammatory bowel disease; Pediatric patients; Pharmacogenetics

Indexed keywords

ALLOPURINOL; AZATHIOPRINE; GLUTATHIONE TRANSFERASE; MERCAPTOPURINE; REACTIVE OXYGEN METABOLITE; GLUTATHIONE; IMMUNOSUPPRESSIVE AGENT;

APOPTOSIS; ARTICLE; CYTOTOXICITY; ENZYME ACTIVITY; GENETIC POLYMORPHISM; HUMAN; INFLAMMATORY BOWEL DISEASE; METABOLISM; OXIDATIVE STRESS; PHARMACOGENETICS; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; ANIMAL; CHEMISTRY; GENETICS; INFLAMMATORY BOWEL DISEASES;

6-MERCAPTOPURINE; ANIMALS; APOPTOSIS; AZATHIOPRINE; GLUTATHIONE; GLUTATHIONE TRANSFERASE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATORY BOWEL DISEASES; OXIDATIVE STRESS; PHARMACOGENETICS; POLYMORPHISM, GENETIC;

EID: 84897526083     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i13.3534     Document Type: Article

References (51)

1. Elion GB. The purine path to chemotherapy. Science 1989; 244: 41-47 [PMID: 2649979]
2. Lin SN, Jessup K, Floyd M, Wang TP, van Buren CT, Caprioli RM, Kahan BD. Quantitation of plasma azathioprine and 6-mercaptopurine levels in renal transplant patients. Transplantation 1980; 29: 290-294 [PMID: 6989049 DOI: 10.109 7/00007890-198004000-00006]
3. Stocco G, Martelossi S, Barabino A, Decorti G, Bartoli F, Montico M, Gotti A, Ventura A. Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease. Inflamm Bowel Dis 2007; 13: 57-64 [PMID: 17206640 DOI: 10.1002/ibd.20004]
4. Dervieux T, Boulieu R. Simultaneous determination of 6-thioguanine and methyl 6-mercaptopurine nucleotides of azathioprine in red blood cells by HPLC. Clin Chem 1998; 44: 551-555 [PMID: 9510860]
5. Stocco G, Cuzzoni E, De Iudicibus S, Franca R, Favretto D, Malusà N, Londero M, Cont G, Bartoli F, Martelossi S, Ventura A, Decorti G. Deletion of glutathione-s-transferase m1 reduces azathioprine metabolite concentrations in young patients with inflammatory bowel disease. J Clin Gastroenterol 2014; 48: 43-51 [PMID: 23787247]
6. Eklund BI, Moberg M, Bergquist J, Mannervik B. Divergent activities of human glutathione transferases in the bioactivation of azathioprine. Mol Pharmacol 2006; 70: 747-754 [PMID: 16717136 DOI: 10.1124/mol.106.025288]
7. Okada Y, Nakamura K, Hiromura K, Nojima Y, Horiuchi R, Yamamoto K. Pro32Thr polymorphism of inosine triphosphate pyrophosphatase gene predicts efficacy of low-dose azathioprine for patients with systemic lupus erythematosus. Clin Pharmacol Ther 2009; 85: 527-530 [PMID: 19129747 DOI: 10.1038/clpt.2008.261]
8. Kim JH, Cheon JH, Hong SS, Eun CS, Byeon JS, Hong SY, Kim BY, Kwon SH, Kim SW, Han DS, Yang SK, Kim WH. Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. J Clin Gastroenterol 2010; 44: e242-e248 [PMID: 20308917]
9. Marsh S, King CR, Ahluwalia R, McLeod HL. Distribution of ITPA P32T alleles in multiple world populations. J Hum Genet 2004; 49: 579-581 [PMID: 15322947 DOI: 10.1007/ s10038-004-0183-y]
10. Piacentini S, Polimanti R, Porreca F, Martínez-Labarga C, De Stefano GF, Fuciarelli M. GSTT1 and GSTM1 gene polymorphisms in European and African populations. Mol Biol Rep 2011; 38: 1225-1230 [PMID: 20563854 DOI: 10.1007/ s11033-010-0221-0]
11. Xu Z, Zhu H, Luk JM, Wu D, Gu D, Gong W, Tan Y, Zhou J, Tang J, Zhang Z, Wang M, Chen J. Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer. Cancer 2012; 118: 5489-5496 [PMID: 22517484 DOI: 10.1002/cncr.27599]
12. Sun P, Qian J, Zhang ZB, Wan JX, Wu F, Jin XP, Fan WW, Lu DR, Zhao NQ, Christiani DC, Xia ZL. Polymorphisms in phase I and phase II metabolism genes and risk of chronic benzene poisoning in a Chinese occupational population. Carcinogenesis 2008; 29: 2325-2329 [PMID: 18784359 DOI: 10.1093/carcin/bgn208]
13. Coles BF, Morel F, Rauch C, Huber WW, Yang M, Teitel CH, Green B, Lang NP, Kadlubar FF. Effect of polymorphism in the human glutathione S-transferase A1 promoter on hepatic GSTA1 and GSTA2 expression. Pharmacogenetics 2001; 11: 663-669 [PMID: 11692074 DOI: 10.1097/00008571-200111000- 00004]
14. Ping J, Wang H, Huang M, Liu ZS. Genetic analysis of glutathione S-transferase A1 polymorphism in the Chinese population and the influence of genotype on enzymatic properties. Toxicol Sci 2006; 89: 438-443 [PMID: 16280386 DOI: 10.1093/toxsci/kfj037]
15. Silva SN, Azevedo AP, Teixeira V, Pina JE, Rueff J, Gaspar JF. The role of GSTA2 polymorphisms and haplotypes in breast cancer susceptibility: a case-control study in the Portuguese population. Oncol Rep 2009; 22: 593-598 [PMID: 19639209]
16. Tetlow N., Board PG. Functional polymorphism of human glutathione transferase A2. Pharmacogenetics 2004; 14: 111-116 [PMID: 15077012 DOI: 10.1097/00008571-200402000-00005]
17. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005; 45: 51-88 [PMID: 15822171 DOI: 10.1146/annurev.pharmtox.45.120403.095857]
18. Zhang ZJ, Hao K, Shi R, Zhao G, Jiang GX, Song Y, Xu X, Ma J. Glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a HuGE review and metaanalysis. Am J Epidemiol 2011; 173: 847-857 [PMID: 21436184 DOI: 10.1093/aje/kwq480]
19. García-Closas M, Malats N, Silverman D, Dosemeci M, Kogevinas M, Hein DW, Tardón A, Serra C, Carrato A, García- Closas R, Lloreta J, Castaño-Vinyals G, Yeager M, Welch R, Chanock S, Chatterjee N, Wacholder S, Samanic C, Torà M, Fernández F, Real FX, Rothman N. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 2005; 366: 649-659 [PMID: 16112301 DOI: 10.1016/ S0140-6736(05)67137-1]
20. Chen CL, Liu Q, Pui CH, Rivera GK, Sandlund JT, Ribeiro R, Evans WE, Relling MV. Higher frequency of glutathione S-transferase deletions in black children with acute lymphoblastic leukemia. Blood 1997; 89: 1701-1707 [PMID: 9057653]
21. Kaplowitz N. Enzymatic thiolysis of azathioprine in vitro. Biochem Pharmacol 1976; 25: 2421-2426 [PMID: 11807]
22. von Bahr C, Glaumann H, Gudas J, Kaplowitz N. Inhibition of hepatic metabolism of azathioprine by furosemide in human liver in vitro. Biochem Pharmacol 1980; 29: 1439-1441 [PMID: 7396978 DOI: 10.1016/0006-2952(80)90442-6]
23. Kaplowitz N, Kuhlenkamp J. Inhibition of hepatic metabolism of azathioprine in vivo. Gastroenterology 1978; 74: 90-92 [PMID: 618434]
24. Kaplowitz N. Interaction of azathioprine and glutathione in the liver of the rat. J Pharmacol Exp Ther 1977; 200: 479-486 [PMID: 850124]
25. O'Donovan P, Perrett CM, Zhang X, Montaner B, Xu YZ, Harwood CA, McGregor JM, Walker SL, Hanaoka F, Karran P. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2005; 309: 1871-1874 [PMID: 16166520]
26. Hemmens VJ, Moore DE. Photochemical sensitization by azathioprine and its metabolites--I. 6-Mercaptopurine. Photochem Photobiol 1986; 43: 247-255 [PMID: 3703958 DOI: 10.1111/j.1751-1097.1986.tb05601.x]
27. Lee AU, Farrell GC. Mechanism of azathioprine-induced injury to hepatocytes: roles of glutathione depletion and mitochondrial injury. J Hepatol 2001; 35: 756-764 [PMID: 11738103 DOI: 10.1016/S0168-8278(01)00196-9]
28. Tapner MJ, Jones BE, Wu WM, Farrell GC. Toxicity of low dose azathioprine and 6-mercaptopurine in rat hepatocytes. Roles of xanthine oxidase and mitochondrial injury. J Hepatol 2004; 40: 454-463 [PMID: 15123360 DOI: 10.1016/ j.jhep.2003.11.024]
29. Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Curr Pharm Des 2005; 11: 4145-4151 [PMID: 16375736 DOI: 10.2174/138161205774913255]
30. Blaker PA, Arenas-Hernandez M, Smith MA, Shobowale- Bakre EA, Fairbanks L, Irving PM, Sanderson JD, Marinaki AM. Mechanism of allopurinol induced TPMT inhibition. Biochem Pharmacol 2013; 86: 539-547 [PMID: 23770457 DOI: 10.1016/j.bcp.2013.06.002]
31. Armstrong JS, Steinauer KK, Hornung B, Irish JM, Lecane P, Birrell GW, Peehl DM, Knox SJ. Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line. Cell Death Differ 2002; 9: 252-263 [PMID: 11859408 DOI: 10.1038/sj.cdd.4400959]
32. Markovic J, Mora NJ, Broseta AM, Gimeno A, de-la- Concepción N, Viña J, Pallardó FV. The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts. PLoS One 2009; 4: e6413 [PMID: 19641610 DOI: 10.1371/journal. pone.0006413]
33. Langer C, Jürgensmeier JM, Bauer G. Reactive oxygen species act at both TGF-beta-dependent and -independent steps during induction of apoptosis of transformed cells by normal cells. Exp Cell Res 1996; 222: 117-124 [PMID: 8549653 DOI: 10.1006/excr.1996.0015]
34. Irwin ME, Rivera-Del Valle N, Chandra J. Redox control of leukemia: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2013; 18: 1349-1383 [PMID: 22900756]
35. Conour JE, Graham WV, Gaskins HR. A combined in vitro/ bioinformatic investigation of redox regulatory mechanisms governing cell cycle progression. Physiol Genomics 2004; 18: 196-205 [PMID: 15138307 DOI: 10.1152/physiolgenomics. 00058.2004]
36. Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, Lehr HA, Wirtz S, Becker C, Atreya R, Mudter J, Hildner K, Bartsch B, Holtmann M, Blumberg R, Walczak H, Iven H, Galle PR, Ahmadian MR, Neurath MF. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 2003; 111: 1133-1145 [PMID: 12697733]
37. Cho SG, Lee YH, Park HS, Ryoo K, Kang KW, Park J, Eom SJ, Kim MJ, Chang TS, Choi SY, Shim J, Kim Y, Dong MS, Lee MJ, Kim SG, Ichijo H, Choi EJ. Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J Biol Chem 2001; 276: 12749-12755 [PMID: 11278289 DOI: 10.1074/jbc.M005561200]
38. Dorion S, Lambert H, Landry J. Activation of the p38 signaling pathway by heat shock involves the dissociation of glutathione S-transferase Mu from Ask1. J Biol Chem 2002; 277: 30792-30797 [PMID: 12077134 DOI: 10.1074/jbc.M203642200]
39. Romero L, Andrews K, Ng L, O'Rourke K, Maslen A, Kirby G. Human GSTA1-1 reduces c-Jun N-terminal kinase signalling and apoptosis in Caco-2 cells. Biochem J 2006; 400: 135-141 [PMID: 16836488 DOI: 10.1042/BJ20060110]
40. Gilot D, Loyer P, Corlu A, Glaise D, Lagadic-Gossmann D, Atfi A, Morel F, Ichijo H, Guguen-Guillouzo C. Liver protection from apoptosis requires both blockage of initiator caspase activities and inhibition of ASK1/JNK pathway via glutathione S-transferase regulation. J Biol Chem 2002; 277: 49220-49229 [PMID: 12370186 DOI: 10.1074/jbc.M207325200]
41. Matsumaru K, Ji C, Kaplowitz N. Mechanisms for sensitization to TNF-induced apoptosis by acute glutathione depletion in murine hepatocytes. Hepatology 2003; 37: 1425-1434 [PMID: 12774022]
42. Nagai H, Matsumaru K, Feng G, Kaplowitz N. Reduced glutathione depletion causes necrosis and sensitization to tumor necrosis factor-alpha-induced apoptosis in cultured mouse hepatocytes. Hepatology 2002; 36: 55-64 [PMID: 12085349]
43. Guo Y, Lu N, Bai A. Clinical use and mechanisms of infliximab treatment on inflammatory bowel disease: a recent update. Biomed Res Int 2013; 2013: 581631 [PMID: 23484133]
44. Cangemi G, Barabino A, Barco S, Parodi A, Arrigo S, Melioli G. A validated HPLC method for the monitoring of thiopurine metabolites in whole blood in paediatric patients with inflammatory bowel disease. Int J Immunopathol Pharmacol 2012; 25: 435-444 [PMID: 22697075]
45. Teichgräber U, Atreya I, Atreya R, Schwab M, Neurath MF. Infliximab treatment induces levels of the active azathioprine metabolite TGTP in Crohn's disease. Inflamm Bowel Dis 2013; 19: E54-E55 [PMID: 22532373 DOI: 10.1002/ibd.22998]
46. Hofmann U, Heinkele G, Angelberger S, Schaeffeler E, Lichtenberger C, Jaeger S, Reinisch W, Schwab M. Simultaneous quantification of eleven thiopurine nucleotides by liquid chromatography-tandem mass spectrometry. Anal Chem 2012; 84: 1294-1301 [PMID: 22220820 DOI: 10.1021/ ac2031699]
47. Kirchherr H, Shipkova M, von Ahsen N. Improved method for therapeutic drug monitoring of 6-thioguanine nucleo- tides and 6-methylmercaptopurine in whole-blood by LC/MSMS using isotope-labeled internal standards. Ther Drug Monit 2013; 35: 313-321 [PMID: 23666567 DOI: 10.1097/ FTD.0b013e318283ed5d]
48. Zhao W, Jacqz-Aigrain E. Principles of therapeutic drug monitoring. Handb Exp Pharmacol 2011; 205: 77-90 [PMID: 21882106 DOI: 10.1007/978-3-642-20195-0_3]
49. Marsh S, Van Booven DJ. The increasing complexity of mercaptopurine pharmacogenomics. Clin Pharmacol Ther 2009; 85: 139-141 [PMID: 19151640 DOI: 10.1038/clpt.2008.219]
50. Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Hicks JK, Schwab M, Klein TE. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther 2013; 93: 324-325 [PMID: 23422873]
51. Stocco G, De Iudicibus S, Franca R, Addobbati R, Decorti G. Personalized therapies in pediatric inflammatory and autoimmune diseases. Curr Pharm Des 2012; 18: 5766-5775 [PMID: 22726111 DOI: 10.2174/138161212803530853]