Common polymorphisms of cyclooxygenase-2 and prostaglandin E2 receptor and increased risk for acute coronary syndrome in coronary artery disease

Wojciech Szczeklik; Marek Sanak; Pawel Rostoff; Wieslawa Piwowarska; Bogdan Jakiela; Andrew Szczeklik

doi:10.1160/TH08-05-0282

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(05): 893-898
DOI: 10.1160/TH08-05-0282

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Common polymorphisms of cyclooxygenase-2 and prostaglandin E2 receptor and increased risk for acute coronary syndrome in coronary artery disease

Authors

Wojciech Szczeklik

¹Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
Marek Sanak

¹Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
Pawel Rostoff

²Department of Coronary Disease, Institute of Cardiology, Jagiellonian University School of Medicine, Cracow, Poland
Wieslawa Piwowarska

²Department of Coronary Disease, Institute of Cardiology, Jagiellonian University School of Medicine, Cracow, Poland
Bogdan Jakiela

¹Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
Andrew Szczeklik

¹Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland

Abstract

Summary

The arachidonic acid metabolites participate in development of coronary artery disease (CAD) and the plaque’s instability.We assessed two common genetic polymorphisms: of cyclooxyge-nase-2 (COX-2) (COX 2.8473, rs5275) and prostaglandin EP2 receptor gene (uS5, rs708494) in patients with CAD. Out of 1,368 patients screened by coronary arteriography, two groups fulfilled the entry criteria and were studied: stable coronary disease (sCAD, n=125) and acute coronary syndromes (ACS, n=63).They did not differ in the main characteristics.All patients were on aspirin at least seven days prior to the study.In 70 control subjects, the same genotypes were ascertained, expression of cyclooxygenases in peripheral blood monocytes was assessed by flow cytometry, and in-vitro biosynthesis of PGE₂ was measured by mass spectrometry. COX-2 CC homozygotes (variant allele), were more common, while EP2 GG homozygotes (wild-type) were less common in ACS (p=0.03 and p=0.017) than in the sCAD group.A combined genotype characterized by the presence of the wild-type COX2.8743T allele and the wild type homozygous EP2uS5 genotype (TT or CT | GG) decreased risk ratio of ACS in CAD patients (relative risk 0.41;95% confidence interval 0.21–0.81).COX-2 polymorphism in control subjects did not affect the enzyme expression or PGE₂ production by peripheral blood monocytes, but production of PGE₂ increased by 40.1% in the subjects homozygous for EP2 receptor allele uS5A following lipopolysaccharide stimulation. In conclusion, the combined COX-2 (COX 2.8473) and the EP2 receptor (uS5) genotypes seem to influence CAD stability, but in peripheral blood monocytes only EP2 receptor modulates PGE₂ production.

Keywords

Arachidonic acid - coronary artery disease - cyclooxygenase-2 - genetic polymorphisms - prostaglandin E2

Full Text

References

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