Glycoprotein Ibα Polymorphism T145M, Elevated Lipoprotein-Associated Phospholipase A2, and Hypertriglyceridemia Predict Risk for Recurrent Coronary Events in Diabetic Postinfarction Patients

Author:

Corsetti James P.1,Ryan Dan1,Moss Arthur J.2,Rainwater David L.3,Zareba Wojciech2,Sparks Charles E.1

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York

2. Department of Medicine, Cardiology Unit, University of Rochester School of Medicine and Dentistry, Rochester, New York

3. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas

Abstract

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 Ibα (GPIbα) subunit. The study comprised diabetic and nondiabetic patients of the Thrombogenic Factors and Recurrent Coronary Events postinfarction study. Cox proportional hazards multivariable modeling, adjusted for significant clinical covariates, was performed using the polymorphism and metabolic, inflammatory, and thrombogenic blood markers. Nondiabetic 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 (2.91, 1.52–5.56, P = 0.001), and elevated Lp-PLA2 (2.78, 1.45–5.35, P = 0.002). Joint risk (one, two, or three risk factors) expressed as relative outcome rates (compared with no risk factors) were 2.4, 4.0, and 8.2, respectively. We conclude that the M allele of the T145M polymorphism of the GPIbα subunit predicts risk for recurrent coronary events in diabetic postinfarction patients, but not in nondiabetic postinfarction patients, supportive of an important role for platelet hyperactivation in diabetic coronary heart disease.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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