ASSOCIATION OF THE PLATELET GLYCOPROTEIN IIIA PL(A1 A2) GENE POLYMORPHISM TO CORONARY-ARTERY DISEASE BUT NOT TO NONFATAL MYOCARDIAL-INFARCTION IN LOW-RISK PATIENTS/

Background. The platelet membrane glycoprotein IIb/IIIa functions as a receptor for fibrinogen and von Willebrand factor during platelet agg regation. In a small case-control study, evidence has been presented t hat the Pl(A2) allele of the platelet glycoprotein GPIIIa Pl(A1/A2) ge ne polymorphism might be an independent risk factor for acute myocardi al infarction (MI). Methods and Results. We explored the association o f the Pl(A1A2) to the severity of coronary artery disease (CAD), as as sessed angiographically in 2252 male individuals, and to myocardial in farction (MI). The severity of coronary heart disease (CHD) was also e stimated by calculating a CHD score according to Gensini. The Pl(A) ge notype was determined by allele specific restriction digestion. Relati on 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 ext ent, of CAD. Also the CHD scores of Pl(A1)/Pl(A2) genotypes were essen tially the same. However, after exclusion of individuals with high BMI (greater than or equal to 26.9 kg/m(2)) and/or low apoAI (<1.43 g/I) Pl(A2)/Pl(A2) carriers had clearly higher CHD scores than Pl(A1)Pl(A1) genotypes; Pl(A1)Pl(A2) heterozygotes had intermediate values (p <0.0 5). After division of the study population into one group of individua ls without any angiographic signs of CAD (CHD score = 0) and into anot her group of patients with severe CAD (CHD score (greater than or equa l to 120), a strong association of the Pl(A2) allele with severe CAD w as also found in the same low risk groups; e.g. exclusion of persons w ith 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) aiiele to MI: No association was found between Pl(A1)/Pl(A2) genotypes and risk of MI neither in the to tal population nor in low risk subgroups. Conclusions. Whereas no diff erence in the distribution of allele and genotype frequencies between controls and survivors of MI could be detected, the Pl(A2) allele is a ssociated with CHD in low risk patients.