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
Andreas Gardemann (1) , Jörg Humme (1) , Jürgen Stricker (1) , Quoc D. Nguyen (1) , Norbert Katz (1) , Monika Philipp (1) , Harald Tillmanns (2) , Friedrich Wilhelm Hehrlein (3) , Matthias Rau (4) , Werner Haberbosch (4)
From the (1) Institut für Klinische Chemie und Pathobiochemie, (2) Abteilung Kardiologie und Angiologie and (3) Klinik für Herz- und Gefäßchirurgie der Justus-Liebig-Universität Giessen, Giessen, (4) Max-Planck-Institut für Experimentelle und Klinische
Summary Background. The platelet membrane glycoprotein IIb/IIIa functionsas a receptor for fibrinogen and von Willebrand factor during plateletaggregation. In a small case-control study, evidence has been presentedthat the Pl A2 allele of the platelet glycoprotein GPIIIa Pl A1/A2 genepolymorphism might be an independent risk factor for acute myocardialinfarction (MI). Methods and Results. We explored the association ofthe Pl A1A2 to the severity of coronary artery disease (CAD), as assessedangiographically in 2252 male individuals, and to myocardial infarction(MI). The severity of coronary heart disease (CHD) was also estimatedby calculating a CHD score according to Gensini. The Pl A genotypewas determined by allele specific restriction digestion. Relation of thePl A2 allele to CAD: In the total population, the frequency of the Pl A2allele was not associated to the presence or to the extent of CAD. Alsothe CHD scores of Pl A1 /Pl A2 genotypes were essentially the same.However, after exclusion of individuals with high BMI ($26.9 kg/m 2 )and/or low apoAI (,1.43 g/l) Pl A2 Pl A2 carriers had clearly higher CHDscores than Pl A1 Pl A1 genotypes; Pl A1 Pl A2 heterozygotes had inter-mediatevalues (p ,0.05). After division of the study population intoone group of individuals without any angiographic signs of CAD (CHDscore = 0) and into another group of patients with severe CAD (CHDscore ($120), a strong association of the Pl A2 allele with severe CADwas also found in the same low risk groups; e.g. exclusion of personswith 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 associationwas found between Pl A1 /Pl A2 genotypes and risk of MI neither in thetotal population nor in low risk subgroups.Conclusions. Whereas no difference in the distribution of allele andgenotype frequencies between controls and survivors of MI could bedetected, the Pl A2 allele is associated with CHD in low risk patients.