title: 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 HbA1c, 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.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Zietz
authors.forename: C
authors.initials: C
authors.lastname: Buechler
authors.forename: W
authors.initials: W
authors.lastname: Drobnik
authors.forename: H
authors.initials: H
authors.lastname: Herfarth
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: A
authors.initials: A
authors.lastname: Schäffler
mesh_terms: D000368:Aged; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018709:Statistics, Nonparametric
chemical_list: D017395:Plasminogen Activator Inhibitor 1