Platelet glycoprotein Ib alpha 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) l b-IX-V receptor complexes play a key role in the initial adhesion of platel ets to collagen during the formation of a coronary thrombus. The HPA-2 (Thr 145 Met) and VNTR polymorphisms of the gene for GP Iba have been studied pr eviously in hospitalized patients with acute coronary syndromes. The signif icance of these polymorphisms in victims of sudden cardiac death is not kno wn. 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, wh ich 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 alm ost complete linkage disequilibrium. Men with acute MI (n = 80) and coronar y thrombosis (n = 65) were more likely to be carriers of the HPA-2 Met alle le (OR 2.0 and 2.6, respectively, P < 0.005 for both) than were control sub jects who died of noncardiac causes (n = 367). In men < 55 years old, the M et allele was overrepresented (OR 2.2) among victims of SCD ( n = 98) compa red with control subjects (n = 249). In men < 55 years old, 17 of 29 men wi th 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 ha d died of noncardiac causes (ORs 5.6 and 9.2, respectively). Similar associ ations 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.