PMID- 28552948
OWN - NLM
STAT- MEDLINE
DCOM- 20170921
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney 
      injury following cardiac surgery.
PG  - e0175292
LID - 10.1371/journal.pone.0175292 [doi]
LID - e0175292
AB  - Twenty to thirty percent of patients undergoing cardiac surgery develop acute 
      kidney injury (AKI). In mice, inhibition of soluble epoxide hydrolase (sEH) 
      attenuates renal injury following ischemia-reperfusion. We tested the hypothesis 
      that functional variants of EPHX2, encoding sEH, are associated with AKI after 
      cardiac surgery. We genotyped patients in two independent cardiac surgery cohorts 
      for functional EPHX2 polymorphisms, Lys55Arg and Arg287Gln, and determined AKI 
      using Acute Kidney Injury Network criteria. The 287Gln variant was not associated 
      with AKI. In the discovery cohort, the gain-of-function 55Arg variant was 
      associated with an increased incidence of AKI in univariate (p = 0.03) and 
      multivariable (p = 0.04) analyses. In white patients without chronic kidney 
      disease (CKD), the 55Arg variant was independently associated with AKI with an OR 
      of 2.04 (95% CI 0.95-4.42) for 55Arg heterozygotes and 31.53 (1.57-633.19) for 
      homozygotes (p = 0.02), after controlling for age, sex, body mass index, baseline 
      estimated glomerular filtration rate, and use of cardiopulmonary bypass. These 
      findings were replicated in the second cardiac surgery cohort. 12,13- and total- 
      dihydroxyoctadecanoic acids (DiHOME): epoxyoctadecanoic acids (EpOME) ratios were 
      increased in EPHX2 55Arg variant carriers, consistent with increased hydrolase 
      activity. The EPHX2 Lys55Arg polymorphism is associated with AKI following 
      cardiac surgery in patients without preexisting CKD. Pharmacological strategies 
      to decrease sEH activity might decrease postoperative AKI.
FAU - Shuey, Megan M
AU  - Shuey MM
AD  - Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, 
      Tennessee, United States of America.
FAU - Billings, Frederic T 4th
AU  - Billings FT 4th
AD  - Department of Anesthesiology, Vanderbilt University School of Medicine and 
      Vanderbilt University Medical Center, Nashville, Tennessee, United States of 
      America.
AD  - Department of Medicine, Vanderbilt University School of Medicine and Vanderbilt 
      University Medical Center, Nashville, Tennessee, United States of America.
FAU - Wei, Shouzou
AU  - Wei S
AD  - Department of Medicine, Vanderbilt University School of Medicine and Vanderbilt 
      University Medical Center, Nashville, Tennessee, United States of America.
FAU - Milne, Ginger L
AU  - Milne GL
AD  - Department of Medicine, Vanderbilt University School of Medicine and Vanderbilt 
      University Medical Center, Nashville, Tennessee, United States of America.
FAU - Nian, Hui
AU  - Nian H
AD  - Department of Biostatistics, Vanderbilt University School of Medicine and 
      Vanderbilt University Medical Center, Nashville, Tennessee, United States of 
      America.
FAU - Yu, Chang
AU  - Yu C
AD  - Department of Biostatistics, Vanderbilt University School of Medicine and 
      Vanderbilt University Medical Center, Nashville, Tennessee, United States of 
      America.
FAU - Brown, Nancy J
AU  - Brown NJ
AD  - Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, 
      Tennessee, United States of America.
AD  - Department of Medicine, Vanderbilt University School of Medicine and Vanderbilt 
      University Medical Center, Nashville, Tennessee, United States of America.
LA  - eng
GR  - K23 GM102676/GM/NIGMS NIH HHS/United States
GR  - P01 DK038226/DK/NIDDK NIH HHS/United States
GR  - R01 GM112871/GM/NIGMS NIH HHS/United States
GR  - UL1 RR024975/RR/NCRR NIH HHS/United States
PT  - Journal Article
DEP - 20170526
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.3.2.10 (EPHX2 protein, human)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acute Kidney Injury/*etiology/genetics/physiopathology
MH  - Aged
MH  - Cohort Studies
MH  - Coronary Artery Bypass/*adverse effects
MH  - Eicosapentaenoic Acid/blood/metabolism
MH  - Epoxide Hydrolases/chemistry/*genetics
MH  - Female
MH  - Genotype
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Incidence
MH  - Lysine/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
PMC - PMC5446112
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/05/30 06:00
MHDA- 2017/09/22 06:00
PMCR- 2017/05/26
CRDT- 2017/05/30 06:00
PHST- 2016/11/03 00:00 [received]
PHST- 2017/03/23 00:00 [accepted]
PHST- 2017/05/30 06:00 [entrez]
PHST- 2017/05/30 06:00 [pubmed]
PHST- 2017/09/22 06:00 [medline]
PHST- 2017/05/26 00:00 [pmc-release]
AID - PONE-D-16-43816 [pii]
AID - 10.1371/journal.pone.0175292 [doi]
PST - epublish
SO  - PLoS One. 2017 May 26;12(5):e0175292. doi: 10.1371/journal.pone.0175292. 
      eCollection 2017.