Role of the 4G/5G Polymorphism of PAI-1 Gene Promoter on PAI-1 Levels in Obese Patients

Maria Teresa Sartori; Roberto Vettor; Giovanni De Pergola; Vito De Mitrio; Graziella Saggiorato; Paolo Della Mea; Giovanni Maurizio Patrassi; Anna Maria Lombardi; Roberto Fabris; Antonio Girolami

doi:10.1055/s-0037-1616045

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 86(05): 1161-1169
DOI: 10.1055/s-0037-1616045

Review Article

Schattauer GmbH

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

Maria Teresa Sartori

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, Italy

,

Roberto Vettor

²Medical Therapy, University of Padua, Italy

,

Giovanni De Pergola

³Endocrinology and Metabolic Diseases, Italy

,

Vito De Mitrio

⁴Hemostasis and Thrombosis Center, University of Bari, Italy

,

Graziella Saggiorato

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, Italy

,

Paolo Della Mea

²Medical Therapy, University of Padua, Italy

,

Giovanni Maurizio Patrassi

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, Italy

,

Anna Maria Lombardi

²Medical Therapy, University of Padua, Italy

,

Roberto Fabris

²Medical Therapy, University of Padua, Italy

,

Antonio Girolami

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, Italy

› Institutsangaben

Abstract

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

Volltext

Referenzen

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