Summary
As PAI-1, a cardiovascular risk factor linked to insulin-resistance, may be influenced
by a 4G/5G gene polymorphism in disease states, we studied both PAI-1 plasma concentration
(PAI-1:Ag) and 4G/5G polymorphism, and their relationship with anthropometric and
endocrine-metabolic parameters in 93 obese patients and 79 lean normal subjects. In
obese patients PAI-1:Ag levels were significantly increased, namely in males and in
those with central obesity, and tightly related to the insulin-resistance parameters.
In obese patients the 4G/5G polymorphism was a determinant of PAI-1:Ag levels, which
were highest in 4G/4G, intermediate in 4G/5G and lowest in 5G/5G genotype carriers.
PAI-1:Ag levels were significantly associated with most of anthropometric and endocrine-metabolic
parameters only in 4G allele obese carriers. Moreover, only in patients with central
obesity was the relationship between genotype and PAI-1 concentration 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 their lean counterparts.
In conclusion, the 4G/5G polymorphism may influence PAI-1 expression in obesity, with
a crucial role in central but not peripheral adiposity. Since subjects with central
obesity are at high risk for cardiovascular disease, the effects of the 4G/5G polymorphism
on PAI-1 concentration may further enhance this risk.
Keywords
PAI-1 - PAI-1 gene polymorphism - obesity - insulin-resistance - risk markers