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IMPDH1 Gene Polymorphisms and Association With Acute Rejection in Renal Transplant Patients
Author(s) -
Wang J,
Yang JW,
Zeevi A,
Webber SA,
Girnita DM,
Selby R,
Fu J,
Shah T,
Pravica V,
Hutchinson IV,
Burckart GJ
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100347
Subject(s) - renal transplant , medicine , association (psychology) , transplantation , psychology , psychotherapist
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. Clinical Pharmacology & Therapeutics (2008); 83 , 5, 711–717. doi: 10.1038/sj.clpt.6100347