Platelet glycoprotein Ibα HPA-2 Met/VNTR B haplotype as a genetic predictor of myocardial infarction and sudden cardiac death

Background-Sudden cardiac death (SCD) is one of the leading manifestations of coronary heart disease in early middle age. Platelet glycoprotein (GP) lb-IX-V receptor complexes play a key role in the initial adhesion of platelets to collagen during the formation of a coronary thrombus. The HPA-2 (Thr145 Met) and VNTR polymorphisms of the gene for GP Iba have been studied previously in hospitalized patients with acute coronary syndromes. The significance of these polymorphisms in victims of sudden cardiac death is not known. Methods and Results-The association of these 2 polymorphisms with coronary atherosclerosis, coronary artery stenosis, coronary thrombosis, myocardial infarction (MI), and SCD was studied in the Helsinki Sudden Death Study, which comprised 2 large autopsy series, collected 10 years apart during 1981 to 1982 and 1991 to 1992, of 700 middle-aged white Finnish men who suffered sudden or violent out-of-hospital death. The 2 polymorphisms showed an almost complete linkage disequilibrium. Men with acute MI (n = 80) and coronary thrombosis (n = 65) were more likely to be carriers of the HPA-2 Met allele (OR 2.0 and 2.6, respectively, P < 0.005 for both) than were control subjects who died of noncardiac causes (n = 367). In men < 55 years old, the Met allele was overrepresented (OR 2.2) among victims of SCD ( n = 98) compared with control subjects (n = 249). In men < 55 years old, 17 of 29 men with acute MI (58.6%) and 16 of 23 men with coronary thrombosis (69.6%) were carriers of the HPA-2 Met allele compared with the 49 of 249 (19.7%) who had died of noncardiac causes (ORs 5.6 and 9.2, respectively). Similar associations were observed in the separate analyses of both autopsy series. Conclusions-Our results suggest that the HPA-2 Met/VNTR B haplotype of the platelet von Willebrand factor and thrombin receptor protein GP lb-V-IX may be considered to be a major risk factor of coronary thrombosis, fatal MI, and SCD in early middle age.