title: Glycoprotein Ibalpha polymorphism T145M, elevated lipoprotein-associated phospholipase A2, and hypertriglyceridemia predict risk for recurrent coronary events in diabetic postinfarction patients.
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 Ibalpha (GPIbalpha) 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 A(2) (Lp-PLA(2)). 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-PLA(2) (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 GPIbalpha 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. james_corsetti@urmc.rochester.edu
authors.forename: James P
authors.initials: JP
authors.lastname: Corsetti
authors.forename: Dan
authors.initials: D
authors.lastname: Ryan
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Charles E
authors.initials: CE
authors.lastname: Sparks
mesh_terms: D019943:Amino Acid Substitution; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D005260:Female; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012008:Recurrence; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D008074:Lipoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D002784:Cholesterol; D010741:Phospholipases A; D054467:Phospholipases A2