title: IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients.
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.
authors.affiliation: Department of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: J W
authors.initials: JW
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Zeevi
authors.forename: S A
authors.initials: SA
authors.lastname: Webber
authors.forename: D M
authors.initials: DM
authors.lastname: Girnita
authors.forename: R
authors.initials: R
authors.lastname: Selby
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.forename: T
authors.initials: T
authors.lastname: Shah
authors.forename: V
authors.initials: V
authors.lastname: Pravica
authors.forename: I V
authors.initials: IV
authors.lastname: Hutchinson
authors.forename: G J
authors.initials: GJ
authors.lastname: Burckart
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide
chemical_list: D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; D009173:Mycophenolic Acid