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Open Access Research article

Gene sequence variations of the platelet P2Y12 receptor are associated with coronary artery disease

Ugo Cavallari1, Elisabetta Trabetti1*, Giovanni Malerba1, Michele Biscuola1, Domenico Girelli2, Oliviero Olivieri2, Nicola Martinelli2, Dominick J Angiolillo3, Roberto Corrocher2 and Pier Franco Pignatti1

Author Affiliations

1 Department of Mother and Child and of Biology-Genetics, Section of Biology and Genetics, University of Verona, Verona, Italy

2 Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy

3 Division of Cardiology, University of Florida-Shands Jacksonville, FL USA

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BMC Medical Genetics 2007, 8:59  doi:10.1186/1471-2350-8-59

Published: 5 September 2007

Abstract

Background

The platelet P2Y12 receptor plays a key role in platelet activation. The H2 haplotype of the P2Y12 receptor gene (P2RY12) has been found to be associated with maximal aggregation response to adenosine diphosphate (ADP) and with increased risk for peripheral arterial disease. No data are available on its association with coronary artery disease (CAD).

Methods

The H2 haplotype of the P2RY12 was determined in 1378 unrelated patients of both sexes selected according to the presence of significant coronary artery disease (CAD group) or having normal coronary angiogram at cardiac catheterization (CAD-free group). Significant coronary artery disease was angiographically determined, and was defined as a greater than 50% visually estimated luminal diameter stenosis in at least one major epicardial coronary artery.

Results

In the studied population 71.9% had CAD (n = 991) and 28.1% had normal coronary angiogram (n = 387). H2 haplotype carriers were more frequent in the CAD group (p = 0.03, OR = 1.36, 95%CI = 1.02–1.82). The H2 haplotype was significantly associated with CAD in non-smokers (p = 0.007, OR = 1.83 95%CI = 1.17–2.87), but not in smokers. The association remained significant after adjustment for other covariates (age, triglycerides, HDL, hypertension, diabetes) by multivariate logistic regression (p = 0.004, OR = 2.32 95%CI = 1.30–4.15).

Conclusion

Gene sequence variations of the P2Y12 receptor gene are associated with the presence of significant CAD, particularly in non-smoking individuals.