The 4G/5G polymorphism of the plasminogen activator inhibitor gene is associated with the time course of progression to acute coronary syndromes.

The 4G allele of the plasminogen activator inhibitor (PAI-I) gene is associated with increased PAI-I levels. Increased PAI-I levels have been reported to be associated with atherothrombotic events. However, the significance of the 4G/5G polymorphism of the PAI-I gene in the pathogenesis of ischemic heart diseases has not been determined. We assessed the 4G/5G polymorphism of the PAI-I gene in 500 subjects including 148 normal controls, 23 subjects with normal coronary arteries, 28 subjects with a paradoxical acetylcholine response, 97 subjects with angina pectoris (AP) and 204 subjects with myocardial infarction (MI). We assessed the length of time between the first anginal pain and the onset of acute coronary syndromes (ACS) in the AP and MI subjects. Subjects who developed ACS within 2 months from the first anginal pain were categorized to have a rapid progression to ACS, and subjects who had had stable anginal pain more than 2 months were placed in the non-ACS group. Subjects in the ACS group were younger than those in non-ACS group (P = 0.012) The frequency of the 5G/5G genotype of the PAI-I gene was lower in the ACS (0.228) than in the non-ACS group (0.093) (P = 0.003). Multiple logistic analyses revealed that a younger age (P = 0.028, odds ratio = 1.03) and the (4G/5G + 4G/4G) genotype of the PAI-I gene (P = 0.008, odds ratio = 2.68) were associated with the ACS group. We also assessed plasma PAI-I antigen levels in 78 subjects. Plasma PAI-I antigen levels in the non-ACS group were significantly lower than those in the ACS group (P = 0.050). Multiple regression analyses revealed that plasma PAI-I levels were determined by plasma insulin (P < 0.001) and the genotype of the PAI-I gene (P = 0.019). Higher plasma insulin levels and the (4G/5G + 4G/4G) genotype of the PAI-I gene were associated with higher plasma PAI-I levels. The 4G/5G polymorphism of the PAI-I gene influenced not only plasma PAI-I antigen levels but also the time course of the progression to ACS in patients with coronary atherosclerosis.