A novel variant L263F in human inosine 5???-monophosphate dehydrogenase 2 is associated with diminished enzyme activity (original) (raw)

Abstract

Background and objective Inosine 5 0 -monophosphate dehydrogenase 2 is required for purine synthesis in activated lymphocytes. Variants in the IMPDH2 gene may account for the large inter-individual variability in baseline enzyme activity, immunosuppressive efficacy and side effects in transplant recipients receiving mycophenolic acid. Therefore, the objective of this study was to identify and functionally characterize IMPDH2 variants.

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References (37)

  1. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 2000; 47:85-118.
  2. Meriggioli MN, Rowin J, Richman JG, Leurgans S. Mycophenolate mofetil for myasthenia gravis: a double-blind, placebo-controlled pilot study. Ann N Y Acad Sci 2003; 998:494-499.
  3. Provan D, Moss AJ, Newland AC, Bussel JB. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol 2006; 81:19-25.
  4. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353:2219-2228.
  5. Millan O, Brunet M, Martorell J, Garcia F, Vidal E, Rojo I, et al. Pharmacokinetics and pharmacodynamics of low dose mycophenolate mofetil in HIV-infected patients treated with abacavir, efavirenz and nelfinavir. Clin Pharmacokinet 2005; 44:525-538.
  6. Sankatsing SU, Hoggard PG, Huitema AD, Sparidans RW, Kewn S, Crommentuyn KM, et al. Effect of mycophenolate mofetil on the pharmacokinetics of antiretroviral drugs and on intracellular nucleoside triphosphate pools. Clin Pharmacokinet 2004; 43:823-832.
  7. Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 1996; 51:278-298.
  8. Zaza G, Yang W, Kager L, Cheok M, Downing J, Pui CH, et al. Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesis. Blood 2004; 104:1435-1441.
  9. Gandhi V, Keating MJ, Bate G, Kirkpatrick P. Nelarabine. Nat Rev Drug Discovery 2006; 5:17-18.
  10. Carr SF, Papp E, Wu JC, Natsumeda Y. Characterization of human type I and type II IMP dehydrogenases. J Biol Chem 1993; 268:27286-27290.
  11. Zimmermann AG, Wright KL, Ting JP, Mitchell BS. Regulation of inosine-5 0 - monophosphate dehydrogenase type II gene expression in human T cells. Role for a novel 5 0 palindromic octamer sequence. J Biol Chem 1997; 272:22913-22923.
  12. Sanquer S, Breil M, Baron C, Dhamane D, Astier A, Lang P. Induction of inosine monophosphate dehydrogenase activity after long-term treatment with mycophenolate mofetil. Clin Pharmacol Ther 1999; 65:640-648.
  13. Jain J, Almquist SJ, Ford PJ, Shlyakhter D, Wang Y, Nimmesgern E, et al. Regulation of inosine monophosphate dehydrogenase type I and type II isoforms in human lymphocytes. Biochem Pharmacol 2004; 67:767-776.
  14. van Gelder T, Shaw LM. The rationale for and limitations of therapeutic drug monitoring for mycophenolate mofetil in transplantation. Transplantation 2005; 80:S244-S253.
  15. Glander P, Braun KP, Hambach P, Bauer S, Mai I, Roots I, et al. Non-radioactive determination of inosine 5 0 -monophosphate dehydro- genase (IMPDH) in peripheral mononuclear cells. Clin Biochem 2001; 34:543-549.
  16. Yatscoff RW, Aspeslet LJ, Gallant HL. Pharmacodynamic monitoring of immunosuppressive drugs. Clin Chem 1998; 44:428-432.
  17. Kelly P, Kahan BD. Review: metabolism of immunosuppressant drugs. Curr Drug Metab 2002; 3:275-287.
  18. Futer O, Sintchak MD, Caron PR, Nimmesgern E, DeCenzo MT, Livingston DJ, et al. A mutational analysis of the active site of human type II inosine 5 0 -monophosphate dehydrogenase. Biochem Biophys Acta 2002; 1594:27-39.
  19. Digits JA, Hedstrom L. Species-specific inhibition of inosine 5 0 - monophosphate dehydrogenase by mycophenolic acid. Biochemistry 1999; 38:15388-15397.
  20. McPhillips CC, Hyle JW, Reines D. Detection of the mycophenolate- inhibited form of IMP dehydrogenase in vivo. Proc Natl Acad Sci U S A 2004; 101:12171-12176.
  21. Cattaneo D, Merlini S, Pellegrino M, Carrara F, Zenoni S, Murgia S, et al. Therapeutic drug monitoring of sirolimus: effect of concomitant immunosuppressive therapy and optimization of drug dosing. Am J Transplant 2004; 4:1345-1351.
  22. Kennan A, Aherne A, Palfi A, Humphries M, McKee A, Stitt A, et al. Identification of an IMPDH1 mutation in autosomal dominant retinitis pigmentosa (RP10) revealed following comparative microarray analysis of transcripts derived from retinas of wild-type and Rho( -/ -) mice. Hum Mol Genet 2002; 11:547-557.
  23. Bowne SJ, Sullivan LS, Mortimer SE, Hedstrom L, Zhu J, Spellicy CJ, et al. Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis. Invest Ophthalmol Vis Sci 2006; 47:34-42.
  24. Grinyo J, Vanrenterghem Y, Nashan B, Vincenti F, Ekberg H, Spleiss O, et al. Association of three polymorphisms with acute rejection after kidney transplantation: an exploratory pharmacogenetic analysis of a randomized multicenter clinical trial (the CAESAR study). Am J Transplantation 2006; 6:410-411.
  25. Bowne SJ, Sullivan LS, Blanton SH, Cepko CL, Blackshaw S, Birch DG, et al. Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa. Hum Mol Genet 2002; 11:559-568.
  26. Farazi T, Leichman J, Harris T, Cahoon M, Hedstrom L. Isolation and characterization of mycophenolic acid-resistant mutants of inosine-5 0 - monophosphate dehydrogenase. J Biol Chem 1997; 272:961-965.
  27. Ikegami T, Natsumeda Y, Weber G. Purification of IMP dehydrogenase from rat hepatoma 3924A. Life Sci 1987; 40:2277-2282.
  28. Hale MD, Nicholls AJ, Bullingham RE, Hene R, Hoitsma A, Squifflet JP, et al. The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Pharmacol Ther 1998; 64:672-683.
  29. Pape L, Ehrich JH, Offner G. Long-term follow-up of pediatric transplant recipients: mycophenolic acid trough levels are not a good indicator for long-term graft function. Clin Transplantation 2004; 18:576-579.
  30. Glander P, Hambach P, Braun KP, Fritsche L, Giessing M, Mai I, et al. Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation. [see comment]. Am J Transplantation 2004; 4:2045-2051.
  31. Vannozzi F, Filipponi F, Di Paolo A, Danesi R, Urbani L, Bocci G, et al. An exploratory study on pharmacogenetics of inosine-monophosphate dehydrogenase II in peripheral mononuclear cells from liver-transplant recipients. Transplant Proc 2004; 36:2787-2790.
  32. Kuypers DRJ, Naesens M, Vanrenterghem Y. MRP 2 gene promoter region single nucleotide polymorphism C-24 T protects renal graft recipients against early liver dysfunction-induced mycophenolic acid underexposure but promotes diarrhea. Am J Transplantation 2006; 6:347.
  33. Hesselink DA, van Hest RM, Mathot RAA, Bonthuis F, Weimar W, de Bruin RWF, et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplantation 2005; 5:987-994.
  34. Kuypers DRJ, Naesens M, Vermeire S, Vanrenterghem Y. The impact of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T on early mycophenolic acid dose-interval exposure in de novo renal allograft recipients. Clin Pharmacol Ther 2005; 78:351-361.
  35. Sintchak MD, Fleming MA, Futer O, Raybuck SA, Chambers SP, Caron PR, et al. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell 1996; 85:921-930.
  36. Nimmesgern E, Black J, Futer O, Fulghum JR, Chambers SP, Brummel CL, et al. Biochemical analysis of the modular enzyme inosine 5 0 - monophosphate dehydrogenase. Protein Exp Purif 1999; 17:282-289.
  37. Ji Y, Gu J, Makhov AM, Griffith JD, Mitchell BS. Regulation of the interaction of inosine monophosphate dehydrogenase with mycophenolic Acid by GTP. J Biol Chem 2006; 281:206-212.