IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients.

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Wang J, Yang JW, Zeevi A, Webber SA, Girnita DM, Selby R, Fu J, Shah T, Pravica V, Hutchinson IV, Burckart GJ

IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients.

Clin Pharmacol Ther. 2008 May;83(5):711-7. Epub 2007 Sep 12.

PubMed ID

17851563 [ View in PubMed

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Abstract

Inosine 5'-monophosphate dehydrogenase 1 (IMPDH1) catalyzes the rate-limiting step of the de novo pathway for purine synthesis and is a major target of the immunosuppressive drug mycophenolic acid (MPA). Few variants of the IMPDH1 gene have been reported. The objective of this study was to identify and characterize IMPDH1 variants to determine whether genetic variation contributes to differences in MPA response and toxicity in transplant patients. Seventeen genetic variants were identified in the IMPDH1 gene with allele frequencies ranging from 0.2 to 42.7%. In this study, 191 kidney transplant patients who received mycophenolate mofetil were genotyped for IMPDH1. Two single-nucleotide polymorphisms, rs2278293 and rs2278294, were significantly associated with the incidence of biopsy-proven acute rejection in the first year post-transplantation. Future studies of the multifactorial nature of acute rejection must consider IMPDH1 polymorphisms in MPA-treated patients.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mycophenolate mofetil	Inosine-5'-monophosphate dehydrogenase 1	Protein	Humans	Yes	Inhibitor Inducer	Details