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Associations between a polymorphism in the gene encoding glycoprotein IIIa and myocardial infarction or coronary
J L Anderson1, G J King, T L Bair
1Department of Medicine, University of Utah and LDS Hospital, Salt Lake City, USA.
Objectives:
The purpose of this study was to determine whether a common variant (PIA2) 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] > 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 PI(A2) 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 PI(A2) 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 PI(A2) variant of the gene encoding GP IIIa is modestly associated (OR approximately 1.5) with nonfatal MI but shows little if any association with CAD per se.
Insights
A common variant (PI*A2) in the glycoprotein IIIa gene shows a modest association with myocardial infarction (MI) risk. However, this genetic factor appears to have little impact on coronary artery disease (CAD) itself.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Thrombosis Research
Background:
- Platelet glycoprotein (GP) IIb/IIIa plays a critical role in thrombus formation, a key event in myocardial infarction (MI).
- Genetic variations in GP IIb/IIIa may influence platelet aggregation and affect the risk of MI and coronary artery disease (CAD).
Purpose of the Study:
- To investigate the association between the PI*A2 variant of the GP IIIa gene and the risk of MI and CAD.
- To determine if genetic differences in GP IIIa influence platelet activation and aggregation, thereby impacting cardiovascular disease risk.
Main Methods:
- Genotyping of the GP IIIa gene (PI*A2 variant) using polymerase chain reaction and restriction enzyme digestion (MspI).
- Analysis of 791 patients undergoing angiography, comparing genotype frequencies between those with and without MI or CAD.
- Calculation of odds ratios (OR) to assess the association between the PI*A2 allele and cardiovascular outcomes, adjusted for standard risk factors.
Main Results:
- The PI*A2 allele was present in 33.8% of MI patients versus 26.9% of controls (OR=1.39, p=0.09).
- For coronary artery disease (CAD), the PI*A2 allele was found in 31.0% of patients with severe stenosis versus 28.2% of controls (OR=1.14, p=0.50).
- Adjusted analyses showed a modest association with MI (OR=1.47, p=0.062) but not with CAD (OR=1.20, p=0.38).
Conclusions:
- The PI*A2 variant of the GP IIIa gene is modestly associated with nonfatal myocardial infarction.
- The association of the PI*A2 variant with coronary artery disease itself appears to be minimal.