Allelic Frequency of the PAI‐1 4G/5G Promoter Polymorphism in Patients with Type 2 Diabetes Mellitus and Lack of Association with PAI‐1 Plasma Levels

Abstract

Plasminogen activator inhibitor‐1 (PAI‐1) levels were found to be associated with obesity, indicating that adipocytes might influence PAI‐1 plasma levels. In addition, the 4G/5G promoter polymorphism of the PAI‐1 gene possibly modulates PAI‐1 gene transcription and, as a consequence, PAI‐1 plasma levels. Metabolic parameters, diabetes complications, PAI‐1 plasma levels, and PAI‐1 promoter genotypes were determined and were tested for correlation in 547 Caucasian patients with type 2 diabetes. Genotyping was performed by using allele‐specific PCR, and PAI‐1 plasma levels were measured in 547 well‐characterized subjects with type 2 diabetes. The allelic frequencies of the polymorphism (0.56 for the 4G‐genotype, 0.44 for the 5G‐genotype) were not different from those observed in nondiabetic controls. The PAI‐1 concentration was positively associated with MI, but not with the 4G/5G polymorphism. Statistical analysis of metabolic parameters, diabetic complications, and the 4G/5G polymorphism revealed that serum fibrinogen levels were significantly higher in the 4G/4G subgroup compared with the 4G/5G and 5G/5G subgroups. The correlation between serum fibrinogen and 4G allele remained significant, even when additional variables, such as gender, age, BMI, duration of diabetes, and HbA_1c, were controlled. In patients with type 2 diabetes mellitus, the PAI‐1 4G/5G promoter polymorphism does not predict PAI‐1 plasma levels and is not associated with common metabolic parameters besides fibrinogen levels.

• PAI‐1
• Promoter
• Polymorphism
• Fibrinogen
• Diabetes

Acknowledgments

The technical assistance of K. Winkler, M. Haas and S. Ammon is highly appreciated. The work was supported by a grant of the German Research Association SCHA 789/2‐3.