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Diabetes Publish Ahead of Print published online ahead of print February 15, 2007
DOI: 10.2337/db06-1573
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Original Research

Glycoprotein Ib{alpha} Polymorphism (T145M), Elevated Lipoprotein-Associated Phospholipase A2, and Hypertriglyceridemia Predict Risk for Recurrent Coronary Events in Diabetic Postinfarction Patients

James P. Corsetti1, Dan Ryan1, Arthur J. Moss2, David L. Rainwater3, Wojciech Zareba2, and Charles E. Sparks1

1Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
2Department of Medicine - Cardiology Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY
3Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX

Correspondence: james_corsetti{at}urmc.rochester.edu

To explore altered platelet function in recurrent coronary event risk among diabetic postinfarction patients, we investigated a function-altering genetic polymorphism (T145M) in the von Willebrand factor binding region of the platelet glycoprotein Ib{alpha} (GPIb{alpha}) subunit. The study comprised diabetic and non-diabetic patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study. Cox proportional hazards multivariable modeling, adjusted for significant clinical covariates, was performed using the polymorphism and metabolic, inflammatory, and thrombogenic blood markers. Non-diabetic patients demonstrated risk for elevated lipoprotein-associated phospholipase A2 (Lp-PLA2). In contrast, diabetic patients demonstrated significant and independent risk for the M allele of the T145M polymorphism (MT plus MM versus TT; hazard ratio (HR), 3.73; 95%CI, 1.90-7.33; p<0.001), hypertriglyceridemia (HR, 2.91; 95%CI, 1.52-5.56; p=0.001), and elevated Lp-PLA2 (HR, 2.78; 95%CI, 1.45-5.35; p=0.002). Joint risk (one, two, or three risk factors) expressed as relative outcome rates (compared to no risk factors) were 2.4, 4.0, and 8.2, respectively. We conclude that the M allele of the T145M polymorphism of the GPIb{alpha} subunit predicts risk for recurrent coronary events in diabetic postinfarction patients, but not in non-diabetic postinfarction patients, supportive of an important role for platelet hyperactivation in diabetic coronary heart disease.


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