Role of the 4G/5G polymorphism of PaI-1 gene promoter on PaI-1 levels in obese patients: influence of fat distribution and insulin-resistance.
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 endocrinemetabolic 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.
Sartori
M T
MT
Department of Medical and Surgical Sciences, University of Padua, Italy. mtsart@unipd.it
Vettor
R
R
De Pergola
G
G
De Mitrio
V
V
Saggiorato
G
G
Della Mea
P
P
Patrassi
G M
GM
Lombardi
A M
AM
Fabris
R
R
Girolami
A
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001824:Body Constitution; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D012737:Sex Factors
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1