title: A 3'-UTR Polymorphism in Soluble Epoxide Hydrolase Gene Is Associated with Acute Rejection in Renal Transplant Recipients.
abstract: OBJECTIVE
  Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms in the gene encoding soluble epoxy hydrolase (EPHX2), which metabolizes EETs to less active compounds, may play a role in the outcome of renal transplantation.
  
  
  METHODS
  In a group of 259 Caucasian renal transplant recipients and 183 deceased donors, we determined the presence of three common EPHX2 SNPs, namely rs41507953 (K55R), rs751141 (R287Q) and rs1042032 A/G. Associations with parameters of graft function and the incidence of acute rejection were retrospectively investigated throughout the first year after grafting by logistic regression adjusting for clinical and demographic variables.
  
  
  RESULTS
  Carriers of the rs1042032 GG genotype displayed significantly lower estimated glomerular filtration rate (eGFR) (38.15 ± 15.57 vs. 45.99 ± 16.05; p = 0.04) and higher serum creatinine values (1.57 ± 0.58 vs. 1.30 ± 0.47 g/dL; p=0.02) one year after grafting, compared to patients carrying the wildtype A-allele. The same GG genotype was also associated to increased risk of acute rejection. Interestingly, this association was observed for the genotype of both recipients [OR =6.34 (1.35-29.90); p = 0.015] and donors [OR = 5.53 (1.10-27.80); p=0.042]. A statistical model including both genotypes along with other meaningful demographic and clinical variables resulted in an increased significance for the association with the recipients' genotype [OR=8.28 (1.21-74.27); p=0.031].
  
  
  CONCLUSIONS
  Our results suggest that genetic variability in the EETs-metabolizing gene, EPHX2, may have a significant impact on the outcome of deceased-donor renal transplantation.
authors.affiliation: Department of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gervasini
authors.affiliation: Department of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Cerrada
authors.affiliation: Molecular Genetics, Laboratory of Medicine, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain; Red de Investigación Renal, Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.affiliation: Service of Immunology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Vergara
authors.affiliation: Service of Nephrology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: García-Pino
authors.affiliation: Service of Nephrology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Alvarado
authors.affiliation: Service of Immunology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Fernández-Cavada
authors.affiliation: Laboratory of Molecular Biology of Renal Disease, Health Research Institute F. Jimenez-Diaz, Universidad Autónoma, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Suárez-Álvarez
authors.affiliation: Service of Nephrology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Barroso
authors.affiliation: Service of Immunology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Doblaré
authors.affiliation: Service of Nephrology, HUCA, Oviedo, Spain; Red de Investigación Renal, Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz-Corte
authors.affiliation: Service of Immunology, HUCA, Oviedo, Spain; Red de Investigación Renal, Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.affiliation: Service of Nephrology, Infanta Cristina University Hospital, Badajoz, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Cubero
mesh_terms: D020413:3' Untranslated Regions; D004851:Epoxide Hydrolases / Q000235:genetics*; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014019:Tissue Donors
chemical_list: D020413:3' Untranslated Regions; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human