A 3’-UTR Polymorphism in Soluble Epoxide Hydrolase Gene Is Associated with Acute Rejection in Renal Transplant Recipients

• Published in: PloS one Vol. 10; no. 7; p. e0133563
• Main Authors: Gervasini, Guillermo, García-Cerrada, Montserrat, Coto, Eliecer, Vergara, Esther, García-Pino, Guadalupe, Alvarado, Raul, Fernández-Cavada, Maria Jesús, Suárez-Álvarez, Beatriz, Barroso, Sergio, Doblaré, Emilio, Díaz-Corte, Carmen, López-Larrea, Carlos, Cubero, Juan Jose
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.07.2015; Public Library of Science (PLoS)
• Subjects: 3' Untranslated Regions; Acids; Arachidonic acid; Bioinformatics; Cardiovascular disease; Creatinine; Cytochrome; Demographic variables; Demographics; Donors; Enzymes; Epidermal growth factor receptors; Epoxide hydrolase; Epoxide Hydrolases - genetics; Gene polymorphism; Genetic engineering; Genetic variability; Genotypes; Glomerular filtration rate; Graft rejection; Graft Rejection - genetics; Grafting; Health risk assessment; Hospitals; Humans; Immunology; Ischemia; Kidney diseases; Kidney Transplantation; Laboratories; Mathematical models; Metabolites; Middle Aged; Nephrology; Oxygenation; Polymorphism; Polymorphism, Single Nucleotide; Rejection; Rodents; Single-nucleotide polymorphism; Statistical analysis; Statistical models; Studies; Tissue Donors; Transplantation; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133563

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. 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. 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]. 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.