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Glycoprotein Ibalpha polymorphism T145M, elevated lipoprotein-associated phospholipase A2, and hypertriglyceridemia
James P Corsetti1, Dan Ryan, Arthur J Moss
1Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. james_corsetti@urmc.rochester.edu
Insights
Diabetic patients with a specific gene variant (T145M M allele) face higher recurrent coronary event risk after heart attack. This platelet GPIbalpha variant, along with hypertriglyceridemia, significantly predicts risk in these patients.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Platelet Biology
Background:
- Recurrent coronary events pose a significant risk for postinfarction patients, particularly those with diabetes.
- Platelet function alterations are implicated in thrombotic events.
- Genetic variations can influence protein function and disease susceptibility.
Purpose of the Study:
- To investigate the association between a specific genetic polymorphism in platelet glycoprotein Ibalpha (GPIbalpha), T145M, and the risk of recurrent coronary events in diabetic and nondiabetic postinfarction patients.
- To identify independent risk factors for recurrent coronary events in these patient groups.
Main Methods:
- The study included diabetic and nondiabetic patients from the Thrombogenic Factors and Recurrent Coronary Events postinfarction study.
- Cox proportional hazards multivariable modeling was used to assess risk.
- Genetic polymorphism (T145M), metabolic, inflammatory, and thrombogenic blood markers were analyzed.
Main Results:
- Nondiabetic patients showed risk associated with elevated lipoprotein-associated phospholipase A(2) (Lp-PLA(2)).
- Diabetic patients demonstrated significant independent risk from the T145M polymorphism M allele (HR 3.73), hypertriglyceridemia (HR 2.91), and elevated Lp-PLA(2) (HR 2.78).
- Joint risk analysis revealed substantially increased relative outcome rates with multiple risk factors (up to 8.2-fold).
Conclusions:
- The M allele of the T145M GPIbalpha polymorphism is a significant predictor of recurrent coronary events in diabetic postinfarction patients.
- Platelet hyperactivation, influenced by genetic factors like the T145M polymorphism, plays a crucial role in the pathophysiology of coronary heart disease in diabetic 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.
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