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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

Diabetes
|February 17, 2007
PubMed

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.

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