Summary

As PAI-1, a cardiovascular risk factor linked to insulin-resistance,may be influenced by a 4G/5G gene polymorphism in disease states, westudied both PAI-1 plasma concentration (PAI-1:Ag) and 4G/5G polymorphism,and their relationship with anthropometric and endocrinemetabolicparameters in 93 obese patients and 79 lean normal subjects.In obese patients PAI-1:Ag levels were significantly increased, namelyin males and in those with central obesity, and tightly related to theinsulin-resistance parameters.In obese patients the 4G/5G polymorphism was a determinant ofPAI-1:Ag levels, which were highest in 4G/4G, intermediate in 4G/5Gand lowest in 5G/5G genotype carriers. PAI-1:Ag levels were significantlyassociated with most of anthropometric and endocrine-metabolicparameters only in 4G allele obese carriers. Moreover, only in patientswith central obesity was the relationship between genotype and PAI-1concentration maintained, with the highest levels in the 4G/4G patients.In each genotype subset of patients with central, but not peripheral,obesity PAI-1:Ag levels were significantly increased compared to theirlean counterparts.In conclusion, the 4G/5G polymorphism may influence PAI-1 expressionin obesity, with a crucial role in central but not peripheraladiposity. Since subjects with central obesity are at high risk forcardiovascular disease, the effects of the 4G/5G polymorphism onPAI-1 concentration may further enhance this risk.