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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

Wojciech Szczeklik
1   Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
,
Marek Sanak
1   Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
,
Pawel Rostoff
2   Department of Coronary Disease, Institute of Cardiology, Jagiellonian University School of Medicine, Cracow, Poland
,
Wieslawa Piwowarska
2   Department of Coronary Disease, Institute of Cardiology, Jagiellonian University School of Medicine, Cracow, Poland
,
Bogdan Jakiela
1   Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
,
Andrew Szczeklik
1   Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland
› Author AffiliationsFinancial support: This paper has been supported by the Polish State Research Grant and by a Jagiellonian University grant.
Further Information

Publication History

Received 05 May 2008

Accepted after major revision 24 August 2008

Publication Date:
22 November 2017 (online)

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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
 

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