The role of inosine-5′-monophosphate dehydrogenase in Thiopurine metabolism in patients with inflammatory bowel disease

Therapeutic Drug Monitoring

Volumn 33, Issue 2, 2011, Pages 200-208

  Haglund, Sofie ^a,b   Vikingsson, Svante ^a   Söderman, Jan ^b   Hindorf, Ulf ^c   Grännö, Christer ^b   Danelius, Margareta ^d   Coulthard, Sally ^e   Peterson, Curt ^a   Almer, Sven ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

^b RYHOV COUNTY HOSPITAL   (Sweden)

^c LUND UNIVERSITY HOSPITAL   (Sweden)

^d ERSTA HOSPITAL   (Sweden)

^e NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

6 TGN; IMPDH; inosine 5 monophosphate dehydrogenase; meTIMP; therapeutic drug monitoring; thiopurines

Indexed keywords

AZATHIOPRINE; CORTICOSTEROID; DIPHTHERIA PERTUSSIS TETANUS HEPATITIS B VACCINE; INOSINATE DEHYDROGENASE; MERCAPTOPURINE; MESALAZINE; MYCOPHENOLIC ACID; THIOGUANOSINE PHOSPHATE; THIOPURINE METHYLTRANSFERASE; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; AGED; ARTICLE; AUTOIMMUNE HEPATITIS; CHILD; COLLAGENOUS COLITIS; CROHN DISEASE; DOWN REGULATION; DRUG METABOLISM; ENZYME ACTIVITY; EOSINOPHILIC COLITIS; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; SCHOOL CHILD; ULCERATIVE COLITIS;

ADOLESCENT; ADRENAL CORTEX HORMONES; ADULT; AGED; AMINOSALICYLIC ACIDS; CHILD; FEMALE; GUANINE NUCLEOTIDES; HEK293 CELLS; HUMANS; IMP DEHYDROGENASE; INFLAMMATORY BOWEL DISEASES; MALE; METHYLTRANSFERASES; MIDDLE AGED; PHENOTYPE; PHOSPHORYLATION; RNA, MESSENGER; THIOINOSINE; THIONUCLEOTIDES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 79953230029     PISSN: 01634356     EISSN: 15363694     Source Type: Journal    
DOI: 10.1097/FTD.0b013e31820b42bb     Document Type: Article

References (59)

1. 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)
2. Elion GB. Symposium on immunosuppressive drugs. Biochemistry and pharmacology of purine analogues. Fed Proc. 1967;26:898-904.
3. Eichelbaum M, Ingelman-Sundberg M, Evans WE. Pharmacogenomics and individualized drug therapy. Annu Rev Med. 2006;57:119-137. (Pubitemid 43261982)
4. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet. 1980;32:651-662. (Pubitemid 10061685)
5. Krynetskaia NF, Krynetski EY, Evans WE. Human RNase H-mediated RNA cleavage from DNA-RNA duplexes is inhibited by 6-deoxythioguanosine incorporation into DNA. Mol Pharmacol. 1999;56:841-848. (Pubitemid 29491188)
6. Maybaum J, Mandel HG. Unilateral chromatid damage: a new basis for 6-thioguanine cytotoxicity. Cancer Res. 1983;43:3852-3856. (Pubitemid 13077716)
7. Tiede I, Fritz G, Strand S, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003;111:1133-1145. (Pubitemid 36519931)
8. 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.
9. Evans WE, Hon YY, Bomgaars L, et al. Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. J Clin Oncol. 2001;8: 2293-2301. (Pubitemid 32366982)
10. 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.
11. Tay BS, Lilley RM, Murray AW, et al. Inhibition of phosphoribosyl pyrophosphate amidotransferase from Ehrlich ascites-tumour cells by thiopurine nucleotides. Biochem Pharmacol. 1969;18:936-938.
12. Dubinsky MC, Lamothe S, Yang HY, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000;118:705-713. (Pubitemid 30171620)
13. Nygaard U, Toft N, Schmiegelow K. Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity. Clin Pharmacol Ther. 2004;75:274-281. (Pubitemid 38471553)
14. Hindorf U, Lindqvist M, Peterson C, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006;55:1423-1431. (Pubitemid 44476786)
15. Dubinsky MC, Yang H, Hassard PV, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology. 2002;122:904-915. (Pubitemid 34267273)
16. 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. (Pubitemid 38971231)
17. Gu JJ, Kaiser-Rogers K, Rao K, et al. Assignment of the human type I IMP dehydrogenase gene (IMPDH1) to chromosome 7q31.3-q32). Genomics. 1994;24:179-181. (Pubitemid 24368763)
18. Kost-Alimova MV, Glesne DA, Huberman E, et al. Assignment1 of inosine'-monophosphate dehydrogenase type 2 (IMPDH2) to human chromosome band 3p21.2 by in situ hybridization. Cytogenet Cell Genet. 1998;82:145-146. (Pubitemid 29002453)
19. Senda M, Natsumeda Y. Tissue-differential expression of two distinct genes for human IMP dehydrogenase (E.C. 1.1. 1.205). Life Sci. 1994;54: 1917-1926. (Pubitemid 24170252)
20. Jain J, Almquist SJ, Ford PJ, et al. Regulation of inosine monophosphate dehydrogenase type I and type II isoforms in human lymphocytes. Biochem Pharmacol. 2004;67:767-776. (Pubitemid 38125261)
21. Stocco G, Cheok MH, Crews KR, et al. Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther. 2009;85:164-172.
22. Bierau J, Lindhout M, Bakker JA. Pharmacogenetic significance of inosine triphosphatase. Pharmacogenomics. 2007;8:1221-1228. (Pubitemid 47578231)
23. Gearry RB, Roberts RL, Barclay ML, et al. Lack of association between the ITPA 94C.A polymorphism and adverse effects from azathioprine. Pharmacogenetics. 2004;14:779-781. (Pubitemid 39552794)
24. Allorge D, Hamdan R, Broly F, et al. ITPA genotyping test does not improve detection of Crohn's disease patients at risk of azathioprine/ 6-mercaptopurine induced myelosuppression. Gut. 2005;54:565. (Pubitemid 40395509)
25. Lin S, McLennan AG, Ying K, et al. Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene. J Biol Chem. 2001;276:18695-18701.
26. von Ahsen N, Oellerich M, Armstrong VW. Characterization of the inosine triphosphatase (ITPA) gene: haplotype structure, haplotype-phenotype correlation and promoter function. Ther Drug Monit. 2008;30:16-22. (Pubitemid 351161094)
27. Haglund S, Taipalensuu J, Peterson C, et al. IMPDH activity in thiopurine-treated patients with inflammatory bowel disease-relation to TPMT activity and metabolite concentrations. Br J Clin Pharmacol. 2008;65:69-77. (Pubitemid 350265173)
28. Sparrow MP, Hande SA, Friedman S, et al. Effect of allopurinol on clinical outcomes in inflammatory bowel disease nonresponders to azathioprine or 6-mercaptopurine. Clin Gastroenterol Hepatol. 2007;5:209-214. (Pubitemid 46216945)
29. Coulthard SA, Hogarth LA, Little M, et al. The effect of thiopurine methyltransferase expression on sensitivity to thiopurine drugs. Mol Pharmacol. 2002;62:102-109. (Pubitemid 34680521)
30. Glander P, Braun KP, Hambach P, et al. Non-radioactive determination of inosine 5'-monophosphate dehydrogenase (IMPDH) in peripheral mononuclear cells. Clin Biochem. 2001;34:543-549. (Pubitemid 34014847)
31. Pettersson B, Almer S, Albertioni F, et al. Differences between children and adults in thiopurine methyltransferase activity and metabolite formation during thiopurine therapy: possible role of concomitant methotrexate. Ther Drug Monit. 2002;24:351-358. (Pubitemid 34553199)
32. Lennard L, Singleton HJ. High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: quantitation of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and 6-methylmercaptopurine metabolites in a single sample. J Chromatogr. 1992;583:83-90.
33. Marsh S, King CR, Ahluwalia R, et al. Distribution of ITPA P32T alleles in multiple world populations. J Hum Genet. 2004;49:579-581. (Pubitemid 39506541)
34. Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol. 1996;91:423-433. (Pubitemid 126733803)
35. Hindorf U, Peterson C, Almer S. Assessment of thiopurine methyltransferase and metabolite formation during thiopurine therapy: results from a large Swedish patient population. Ther Drug Monit. 2004;26: 673-678. (Pubitemid 39579150)
36. Lewis LD, Benin A, Szumlanski CL, et al. Olsalazine and 6-mercaptopurine- related bone marrow suppression: a possible drug-drug interaction. Clin Pharmacol Ther. 1997;62:464-475. (Pubitemid 27475231)
37. 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. (Pubitemid 32989202)
38. Gearry RB, Barclay ML. Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. J Gastroenterol Hepatol. 2005;20:1149-1157. (Pubitemid 41602556)
39. van Asseldonk DP, Sanderson J, de Boer NK, et al. Difficulties and possibilities with thiopurine therapy in inflammatory bowel diseaseproceedings of the first thiopurine task force meeting. Dig Liver Dis. October 8, 2010 [epub ahead of print].
40. Chocair P, Duley J, Simmonds HA, et al. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen. Lancet. 1993;342:83-84. (Pubitemid 23192425)
41. Osterman MT, Kundu R, Lichtenstein GR, et al. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology. 2006;130:1047-1053.
42. Montero C, Duley JA, Fairbanks LD, et al. Demonstration of induction of erythrocyte inosine monophosphate dehydrogenase activity in ribavirintreated patients using a high performance liquid chromatography linked method. Clin Chim Acta. 1995;238:169-178.
43. Parks RE Jr, Crabtree GW, Kong CM, et al. Incorporation of analog purine nucleosides into the formed elements of human blood: erythrocytes, platelets, and lymphocytes. Ann N Y Acad Sci. 1975; 255:412-434.
44. Lennard L, Maddocks JL. Assay of 6-thioguanine nucleotide, a major metabolite of azathioprine, 6-mercaptopurine and 6-thioguanine, in human red blood cells. J Pharm Pharmacol. 1983;35:15-18. (Pubitemid 13211341)
45. Karran P, Attard N. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer. 2008;8:24-36.
46. Konno Y, Natsumeda Y, Nagai M, et al. Expression of human IMP dehydrogenase types I and II in Escherichia coli and distribution in human normal lymphocytes and leukemic cell lines. J Biol Chem. 1991;266:506-509. (Pubitemid 21906152)
47. Stet EH, De Abreu RA, Janssen YP, et al. A biochemical basis for synergism of 6-mercaptopurine and mycophenolic acid in Molt F4, a human malignant T-lymphoblastic cell line. Biochim Biophys Acta. 1993;1180:277-282. (Pubitemid 23033020)
48. Bokkerink JP, Stet EH, De Abreu RA, et al. 6-Mercaptopurine: cytotoxicity and biochemical pharmacology in human malignant T-lymphoblasts. Biochem Pharmacol. 1993;45:1455-1463. (Pubitemid 23108805)
49. Petit E, Langouet S, Akhdar H, et al. Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes. Toxicol In Vitro. 2008;22:632-642.
50. Vethe NT, Bremer S, Bergan S. IMP dehydrogenase basal activity in MOLT-4 human leukaemia cells is altered by mycophenolic acid and 6-thioguanosine. Scand J Clin Lab Invest. 2008;68:277-285. (Pubitemid 351962406)
51. Goldsmith D, Carrey EA, Edbury S, et al. Mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, causes a paradoxical elevation of GTP in erythrocytes of renal transplant patients. Clin Sci (Lond). 2004;107:63-68. (Pubitemid 38932198)
52. Jagodzinski P, Lizakowski S, Smolenski RT, et al. Mycophenolate mofetil treatment following renal transplantation decreases GTP concentrations in mononuclear leucocytes. Clin Sci (Lond). 2004;107:69-74. (Pubitemid 38932199)
53. Liliemark J, Pettersson B, Engberg B, et al. On the paradoxically concentration-dependent metabolism of 6-mercaptopurine in WEHI-3b murine leukemia cells. Cancer Res. 1990;50:108-112. (Pubitemid 20030003)
54. Rowland K, Lennard L, Lilleyman JS. In vitro metabolism of 6-mercaptopurine by human liver cytosol. Xenobiotica. 1999;29:615-628. (Pubitemid 29332746)
55. Duley JA, Florin TH. Thiopurine therapies: problems complexities, and progress with monitoring thioguanine nucleotides. Ther Drug Monit. 2005;27:647-654. (Pubitemid 41437645)
56. Barsotti C, Pesi R, Giannecchini M, et al. Evidence for the involvement of cytosolic 5'-nucleotidase (cN-II) in the synthesis of guanine nucleotides from xanthosine. J Biol Chem. 2005;280:13465-13469. (Pubitemid 40517235)
57. Ansari A, Aslam Z, De Sica A, et al. Influence of xanthine oxidase on thiopurine metabolism in Crohn's disease. Aliment Pharmacol Ther. 2008; 28:749-757.
58. de Boer NK, Wong DR, Jharap B, et al. Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism. Am J Gastroenterol. 2007; 102:2747-2753. (Pubitemid 350179331)
59. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373:1905-1917.