The 4G4G genotype of the plasminogen activator inhibitor 4G/5G gene polymorphism is associated with coronary atherosclerosis in patients at high riskfor this disease

Background. Disturbances in fibrinolytic activity, such as increase in plas minogen activator inhibitor (PAI) activity, have-been linked with an increa sed risk for coronary artery disease (CAD) and myocardial infarction (MI). Since 4G4G homozygotes of an insertion/deletion (4G/5G) gene variation in t he promoter of PAI-I have been shown to have increased levels of PAI-I, we analysed the relation of this gene polymorphism to CAD and MI in a populati on of 2565 participants who underwent coronary angiography for diagnostic p urposes. Results. In the total sample, the PAI-I 4G/4G genotype was associ ated with the presence, but not with the extent of CAD. However, in a subgroup of fo rmer and present smokers (n = 1782) or of individuals with a BMI above the mean value of 26.9 kg x m(-2) (n = 1269), the PAI-I 4G4G genotype was not o nly associated with the presence, but also with the extent of CAD, defined either by the number of diseased vessels or by the CHD score according to G ensini. This observation also applied to other high-risk groups of individu als with high BMI and hypertension (n = 869), of subjects with high fibrino gen plasma levels (> 3.53 g X I-1, mean value) and hypertension (n = 599) a nd of former and present smokers with high fibrinogen and hypertension (n = 452). An association of the gene variation with MI was not detected. Conclusions. The present data indicate that the 4G/4G genotype of the PAI-I gene polymorphism is an independent risk factor for coronary artery diseas e and that the additional presence of major cardiovascular risk factors acc elerates the risk for this disease.