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

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.

SUBMITTER: Oni-Orisan A

PROVIDER: S-EPMC6162147 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Oni-Orisan Akinyemi A Cresci Sharon S Jones Philip G PG Theken Katherine N KN Spertus John A JA Lee Craig R CR

Prostaglandins & other lipid mediators 20180807

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 ...[more]

PMID: 30096423

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Project description:BACKGROUND:Calcification of the arteries of the lower extremities is a very common pathological process, which has an independent significance in the development of cardiovascular diseases. There is evidence that development of calcification of the arteries correlates with a mutation of the MGP protein gene representing by the Thr83Ala polymorphism. AIM:The purpose of the study was to analyse the connection of Thr83Ala polymorphism of the MGP gene with the development of calcification of the arteries of the lower extremities. METHODS:The study involved 80 patients. Half of them had signs of calcification of the arteries of the lower extremities. The allelic Thr83Ala polymorphism of the MGP protein gene was determined by polymerase chain reaction, establishing the presence of calcification of the arteries by radiological and dopplerographic methods. RESULTS:The study aimed to analyse the association of the Thr83Ala polymorphism of the matrix Gla protein gene with the development of calcification of the arteries of the lower extremities. The data obtained suggest that the replacement of threonine by alanine in the 83rd position of the MGP molecule can affect the functional properties of the protein and in particular its anticarcinogenic properties. Although there was no difference in the distribution of different variants of the genotype by Thr83Ala to the MGP gene polymorphism in patients with CA and healthy patients, but in the distribution of genotypes in the comparison groups separated by sex, it was found that in women, carriage of the Ala allele in a homozygous state is a factor, which protects the development of arterial calcination in the elderly and senile. CONCLUSION:Differences in the distribution of different variants of the genotype according to Thr83Ala to the polymorphism of the MGP gene between patients with CAD and healthy patients do not exceed the limits of statistical significance. In the distribution of genotypes in the comparison groups divided by sex, it was found that in women the carrier of the Ala-allele in the homozygous state is a factor that prevents the development of Menkeberg arteriosclerosis in the elderly and old age.

Dataset Information

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

Publications

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

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