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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
1   Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Italy
,
Roberto Vettor
2   Medical Therapy, University of Padua, Italy
,
Giovanni De Pergola
3   Endocrinology and Metabolic Diseases, Italy
,
Vito De Mitrio
4   Hemostasis and Thrombosis Center, University of Bari, Italy
,
Graziella Saggiorato
1   Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Italy
,
Paolo Della Mea
2   Medical Therapy, University of Padua, Italy
,
Giovanni Maurizio Patrassi
1   Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Italy
,
Anna Maria Lombardi
2   Medical Therapy, University of Padua, Italy
,
Roberto Fabris
2   Medical Therapy, University of Padua, Italy
,
Antonio Girolami
1   Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, Italy
› Author Affiliations
Further Information

Publication History

Received 04 January 2001

Accepted after resubmission 04 July 2001

Publication Date:
13 December 2017 (online)

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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
 

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