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.


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).


CONCLUSIONS
The present study suggested that the presence of the rs1042032 variant allele in EPHX2 was associated with a protective role for allograft function.
Lee
S H
SH
Department of Internal Medicine, National Police Hospital, Seoul National University College of Medicine, Seoul, Korea.
Lee
J
J
Cha
R
R
Park
M H
MH
Ha
J W
JW
Kim
S
S
Kim
Y S
YS
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008875:Middle Aged; D016896:Treatment Outcome
D020413:3' Untranslated Regions; D001095:Arachidonic Acids; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human