Document Detail


Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and mycophenolic acid exposure parameters on day 28 after renal transplantation.
MedLine Citation:
PMID:  20136638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The risk of acute rejection in patients with higher exposure to mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), might be due to inosine 5'-monophosphate dehydrogenase (IMPDH) polymorphisms. The correlations with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28 post-transplantation were investigated in 82 Japanese recipients. Renal transplant recipients were given combination immunosuppressive therapy consisting of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12 hr at designated times. There were no significant differences in the incidence of subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure range (AUC > 60 microg x h/ml and C(0 )> or = 1.9 microg/ml), there was a significant difference in the incidence of subclinical acute rejection between IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1 rs2278294 genotype. In the higher daytime MPA exposure range, patients with the IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection. In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute rejection episode tends to be low and the administration of MMF was effective. The risk of subclinical acute rejection for recipients who cannot adapt in therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1 rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism as well as monitoring of MPA plasma concentration after transplantation might help to improve MMF therapy.
Authors:
Hideaki Kagaya; Masatomo Miura; Mitsuru Saito; Tomonori Habuchi; Shigeru Satoh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-02
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  107     ISSN:  1742-7843     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-11-05     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  631-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Akita University Hospital, Akita, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adult
Aged
Area Under Curve
Dose-Response Relationship, Drug
Drug Therapy, Combination
Enzyme Inhibitors / adverse effects*,  metabolism
Female
Genotype
Graft Rejection* / enzymology,  genetics,  immunology
Humans
IMP Dehydrogenase / antagonists & inhibitors,  genetics*
Immunocompromised Host
Immunosuppressive Agents / pharmacokinetics,  therapeutic use
Kidney Transplantation / immunology*
Male
Middle Aged
Mycophenolic Acid / adverse effects*,  analogs & derivatives,  metabolism,  pharmacokinetics,  therapeutic use
Polymorphism, Single Nucleotide*
Tacrolimus / therapeutic use
Young Adult
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Immunosuppressive Agents; 109581-93-3/Tacrolimus; 24280-93-1/Mycophenolic Acid; 9242ECW6R0/mycophenolate mofetil; EC 1.1.1.205/IMP Dehydrogenase; EC 1.1.1.205/IMPDH1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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