title: 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.
abstract: 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.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padua, Italy. mtsart@unipd.it
authors.forename: M T
authors.initials: MT
authors.lastname: Sartori
authors.forename: R
authors.initials: R
authors.lastname: Vettor
authors.forename: G
authors.initials: G
authors.lastname: De Pergola
authors.forename: V
authors.initials: V
authors.lastname: De Mitrio
authors.forename: G
authors.initials: G
authors.lastname: Saggiorato
authors.forename: P
authors.initials: P
authors.lastname: Della Mea
authors.forename: G M
authors.initials: GM
authors.lastname: Patrassi
authors.forename: A M
authors.initials: AM
authors.lastname: Lombardi
authors.forename: R
authors.initials: R
authors.lastname: Fabris
authors.forename: A
authors.initials: A
authors.lastname: Girolami
mesh_terms: 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
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1