Effect of glycoprotein IIIa PlA2 polymorphism on outcome of patients with stable coronary artery disease and effect of smoking

A polymorphism of glycoprotein IIb/IIIa has been associated with myocardial infarction and restenosis after percutaneous coronary intervention. The influence on outcome and the interaction of the PlA1 genotype with classic risk factors for coronary artery disease (CAD) were characterized in patients with chronic CAD followed prospectively for 3 years. PlA1 genotypes were assessed in 592 patients enrolled in the Medical, Angioplasty, or Surgery Study II, a randomized trial comparing treatments for patients with CAD and preserved left ventricular function. The incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization were determined in each genotype group. Risk was assessed with the Cox proportional-hazards model. The clinical characteristics and treatment of each genotype were similar. Although the composite end point tended to be more common in patients with the PlA2 allele, only smokers with the PlA2 allele had a significantly increased incidence of the composite end point (p = 0.01). Moreover, a 2.2-fold increased risk was apparent in smokers with the PlA2 allele (p = 0.03). Thus, taken together, these data provide support for the interaction effect between smoking and the PlA1 gene variant. Smokers with the PlA2 polymorphism of platelet glycoprotein IIIa are at greater risk for subsequent cardiac events in stable coronary disease.