Associations between a polymorphism in the gene encoding glycoprotein IIIa and myocardial infarction or coronary artery disease

OBJECTIVES The purpose of this study was to determine whether a common variant (pI(A2)) Of the membrane glycoprotein (GP) IIIa gene is associated with myocardial infarction (MI) or coronary artery disease (CAD). BACKGROUND Platelet GP IIb/IIIa is believed to play a central role in MI, binding fibrinogen, cross-linking platelets and initiating thrombus formation. Genetically determined differences in binding properties of GP IIb/IIIa might result in changes in platelet activation or aggregation and affect the risk of MI or CAD. METHODS To determine associations (odds ratios [OR]1.5 to 2.0) of genotype with MI or CAD, blood was drawn from 791 patients (pt) undergoing angiography. A 266 base pair fragment of the GP IIIa gene was amplified by the polymerase chain reaction and digested with the MspI restriction enzyme. Genotypes were identified after electrophoresis of digestion products in 1.5% agarose gel. RESULTS Of the 791 pt, 225 had acute (n = 143) or previous MI, and 276 did not have MI or unstable angina. The pIA2 allele was carried by 33.8% of MI pt versus 26.9% of no-MI control subjects, OR = 1.39 (95% CI, 0.95 to 2.04, p = 0.09). Angiographically, 549 pt had severe (>60% coronary stenosis) CAD, and 170 had normal coronary arteries (<10% stenosis). The pIA2 allele was found in 31.0% of CAD pt versus 28.2% of no-CAD control subjects, OR = 1.14 (CI, 0.78 to 1.67, p = 0.50). When adjusted for six standard risk factors, ORs were 1.47 (CI, 0.98 to 2.20, p = 0.062) for MI and 1.20 (CI, 0.80 to 1.81, p = 0.38) for CAD. CONCLUSIONS The PIA2 variant of the gene encoding GP IIIa is modestly associated (OR approximate to 1.5) with nonfatal MI but shows little if any association with CAD per se. (C) 1999 by the American College of Cardiology.