Association between the EPHX2 p.Lys55Arg polymorphism and prognosis following an acute coronary syndrome

Akinyemi Oni-Orisan, Sharon Cresci, Philip G. Jones, Katherine N. Theken, John A. Spertus, Craig R. Lee

Research output: Contribution to journalReview articlepeer-review

Abstract

Inhibition of soluble epoxide hydrolase (sEH, EPHX2) elicits potent cardiovascular protective effects in preclinical models of ischemic cardiovascular disease (CVD), and genetic polymorphisms in EPHX2 have been associated with developing ischemic CVD in humans. However, it remains unknown whether EPHX2 variants are associated with prognosis following an ischemic CVD event. We evaluated the association between EPHX2 p.Lys55Arg and p.Arg287Gln genotype with survival in 667 acute coronary syndrome (ACS) patients. No association with p.Arg287Gln genotype was observed (P = 0.598). Caucasian EPHX2 Arg55 carriers (Lys/Arg or Arg/Arg) had a significantly higher risk of 5-year mortality (adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.01–2.55, P = 0.045). In an independent population of 2712 ACS patients, this association was not replicated (adjusted HR 0.92, 95% CI 0.70–1.21, P = 0.559). In a secondary analysis, Caucasian homozygous Arg55 allele carriers (Arg/Arg) appeared to exhibit a higher risk of cardiovascular mortality (adjusted HR 2.60, 95% CI 1.09–6.17). These results demonstrate that EPHX2 p.Lys55Arg and p.Arg287Gln polymorphisms do not significantly modify survival after an ACS event. Investigation of other sEH metabolism biomarkers in ischemic CVD appears warranted.

Original languageEnglish
Pages (from-to)15-22
Number of pages8
JournalProstaglandins and Other Lipid Mediators
Volume138
DOIs
StatePublished - Sep 2018

Keywords

  • Cardiovascular disease
  • EET
  • Eicosanoids
  • Humans
  • Ischemic
  • Polymorphism
  • Prognosis
  • Soluble epoxide hydrolase

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