The 4G4G genotype of the plasminogen activator inhibitor 4G/5G gene polymorphism is associated with coronary atherosclerosis in patients at high riskfor this disease
A. Gardemann et al., The 4G4G genotype of the plasminogen activator inhibitor 4G/5G gene polymorphism is associated with coronary atherosclerosis in patients at high riskfor this disease, THROMB HAEM, 82(3), 1999, pp. 1121-1126
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.