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An exploratory study on pharmacogenetics of inosine-monophosphate dehydrogenase II in peripheral mononuclear cells from liver-transplant recipients.

Abstract：

:Mycophenolate mofetil (MMF) is an immunosuppressant used for the prophylaxis of rejection in renal, pancreas, and liver transplantation. It inhibits the inducible isoform of the enzyme inosine-monophosphate dehydrogenase (IMPDH II) via its active metabolite mycophenolic acid (MPA). IMPDH II is necessary for de novo purine synthesis in activated lymphocytes. The aims of the present study were to evaluate the feasibility of a real-time polymerase chain reaction (PCR) quantitative assessment of IMPDH II gene expression in liver transplant recipients as well as to provide a preliminary evaluation of possible correlations with drug tolerability. RNA was extracted from peripheral blood mononuclear cells of liver recipients after at least 6 months of MMF administration. IMPDH II gene expression was assessed using quantitative, real-time PCR and normalized using glyceraldheyde-3-phosphate dehydrogenase (GAPDH). Finally, adverse events associated with MMF administration were recorded. Real-time PCR quantitation of IMPDH II gene expression was reliable, sensitive, and specific. The intrapatient variability for both IMPDH II and GAPDH assays was lower than 0.6% in all patients. The results demonstrated a wide interpatient variability, with the mean value +/- standard deviation of 0.949 +/- 0.525 (95% confidence interval, 0.669-1.229) and a median value of 0.797. Patients with treatment-related toxicities displayed a trend to a higher level of IMPDH II expression than those without toxicity (mean, 1.126 vs 0.771). In conclusion, pharmacogenetic analysis of IMPDH II may represent a novel approach to MMF therapeutic monitoring.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Vannozzi F,Filipponi F,Di Paolo A,Danesi R,Urbani L,Bocci G,Catalano G,De Simone P,Mosca F,Del Tacca M

doi

10.1016/j.transproceed.2004.09.070

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

2787-90

issue

9

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(04)01142-X

journal_volume

36

pub_type

杂志文章

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