Genetic Variations in Soluble Epoxide Hydrolase and Graft Function in Kidney Transplantation

Background: Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors that contribute renal protective actions. The aim of this study was to identify the association between genetic variations in soluble epoxide hydrolase (EPHX2, EET-metabolizing enzyme) and kidney allograft dysfunction. Materials and Methods: Data from 204 kidney transplant donor-recipient pairs were examined for polymorphisms of exon 8 (R287Q, rs751141 G/A) and 3′ untranslated region (3′ UTR, rs1042032 A/G) of the EPHX2 gene and correlated with clinical data. Results: The mean duration of follow-up for recipients was 58 ± 45.3 months who were 39 ± 11.8 years old at the time of operation and displayed estimated glomerular filtration rate (eGFR) of 68 ± 16.5 mL/min/1.73 m² at 1 month after transplantation. AA, AG, and GG genotype frequencies in 3′ UTR were 28%, 55%, and 16%, respectively. Twenty-one recipients experienced allograft dysfunction with eGFR <30 mL/min/1.73 m²; 10 had AA genotype of rs1042032 polymorphism (chi-square test; A/A vs A/G+G/G; P = .04). Recipients without rs1042032 polymorphism variant allele showed a significant risk for allograft dysfunction (A/A vs A/G+G/G; P = .04; odds ratio, 2.65; 95% confidence interval [CI], 1.03-6.81). Multivariate analysis of the characteristics of patients using a Cox proportional hazard model showed that the AA genotype of rs1042032 polymorphism was predictive of allograft dysfunction (Hazard Ratio = 3.26; P = .04; 95% CI, 1.08-9.59). Conclusion: The present study suggested that the presence of the rs1042032 variant allele in EPHX2 was associated with a protective role for allograft function.