OBJECTIVES The purpose of this study was to determine whether a common vari
ant (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, b
inding fibrinogen, cross-linking platelets and initiating thrombus formatio
n. Genetically determined differences in binding properties of GP IIb/IIIa
might result in changes in platelet activation or aggregation and affect th
e 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 angiograp
hy. A 266 base pair fragment of the GP IIIa gene was amplified by the polym
erase chain reaction and digested with the MspI restriction enzyme. Genotyp
es were identified after electrophoresis of digestion products in 1.5% agar
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) CA
D, and 170 had normal coronary arteries (<10% stenosis). The pIA2 allele wa
s 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 factor
s, 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 assoc
iated (OR approximate to 1.5) with nonfatal MI but shows little if any asso
ciation with CAD per se. (C) 1999 by the American College of Cardiology.