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

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

Address correspondence and reprint requests to James P. Corsetti, MD, PhD, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Box 626, 601 Elmwood Ave., Rochester, NY 14642. E-mail: james_corsetti{at}urmc.rochester.edu

Abbreviations: apo, apolipoprotein; CAD, coronary artery disease; CHD, coronary heart disease; GP, glycoprotein; Lp-PLA_2, lipoprotein-associated phospholipase A₂; MI, myocardial infarction; PAI-1, plasminogen activator inhibitor-1; SNP, single-nucleotide polymorphism; THROMBO, Thrombogenic Factors and Recurrent Coronary Events

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 (GPIb) 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 GPIb 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.

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