Association of the Platelet Glycoprotein IIIa PI^A1/A2 Gene Polymorphism to Coronary Artery Disease but not to Nonfatal Myocardial Infarction in Low Risk Patients

Summary

Background. The platelet membrane glycoprotein IIb/IIIa functions as a receptor for fibrinogen and von Willebrand factor during platelet aggregation. In a small case-control study, evidence has been presented that the Pl^A2 allele of the platelet glycoprotein GPIIIa Pl^A1/A2 gene polymorphism might be an independent risk factor for acute myocardial infarction (MI). Methods and Results. We explored the association of the Pl^A1A2 to the severity of coronary artery disease (CAD), as assessed angiographically in 2252 male individuals, and to myocardial infarction (MI). The severity of coronary heart disease (CHD) was also estimated by calculating a CHD score according to Gensini. The Pl^A genotype was determined by allele specific restriction digestion. Relation of the Pl^A2 allele to CAD: In the total population, the frequency of the Pl^A2 allele was not associated to the presence or to the extent of CAD. Also the CHD scores of Pl^A1/Pl^A2 genotypes were essentially the same. However, after exclusion of individuals with high BMI (≥26.9 kg/m²) and/or low apoAI (<1.43 g/l) Pl^A2Pl^A2 carriers had clearly higher CHD scores than Pl^A1Pl^A1 genotypes; Pl^A1Pl^A2 heterozygotes had intermediate values (p <0.05). After division of the study population into one group of individuals without any angiographic signs of CAD (CHD score = 0) and into another group of patients with severe CAD (CHD score (≥120), a strong association of the Pl^A2 allele with severe CAD was also found in the same low risk groups; e.g. exclusion of persons with high BMI and low apoAI resulted in an Odds ratio of 5.37 (1.46-19.7) (p <0.02). Relation of the Pl^A2 allele to MI: No association was found between Pl^A1/Pl^A2 genotypes and risk of MI neither in the total population nor in low risk subgroups.

Conclusions. Whereas no difference in the distribution of allele and genotype frequencies between controls and survivors of MI could be detected, the Pl^A2 allele is associated with CHD in low risk patients.

• References

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