Genetic and Metabolic Determinants of Plasminogen Activator Inhibitor 1 (PAI-1) in Tunisian Type 2 Diabetes Patients

Abstract

Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PAI-1 gene and environmental factors. The aim of the study was to examine the determinants of plasma PAI-1 Ag level among type 2 diabetes patients. Methods: 491 Tunisian type 2 diabetes patients had clinical evaluation (weight, high, BMI, Waist Circumference), laboratory investigations including FBG Hb1Ac, cholesterol, triglyceride; HDL-cholesterol was done; plasma PAI-1 antigen level was done with ELISA; −675 4G/5G and −844 G/A polymorphisms of PAI-1 gene was done by PCR-ASA and PCR-RFLP respectively. Results: The mean age for our patients was 58.3 ± 10.5 years; sex-ratio = 0.92; mean PAI-1 level was 34.6 ± 21.3 ng/ml. We didn’t find correlation between PAI-1 level and BMI, but we have found significant correlation between PAI-1 and waist circumference (p = 0.032), most enhanced in men (P = 0.002), T2D patients who have FBG > 11 mmol/l had PAI-1 Ag level higher than those who have FBG < 11 mmol/l (P = 0.034), but no difference found between T2D with high Hb1Ac > 8% and those with Hb1Ac < 8%, significant correlation was seen between PAI-1 level and LDL-cholesterol (P = 0.05), high correlation between PAI-1 Ag level and −675 4G/5G polymorphism genotype was seen, 4G/4G carriers had the highest PAI-1 level, 4G/5G had intermediary level and 5G/5G had the lowest level (P < 0.001). No correlation was seen between PAI-1 Ag level and −844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was −675 4G/5G polymorphism (regression coefficient β = 4.6, P < 0.01). Conclusion: the present study identifies −675 4G/5G not −844 G/A polymorphism of PAI gene as the principal determinant of plasma PAI-1 level in Tunisian T2D patients, the android fat distribution, dyslipidemia and hyperglycemia play a modest role in this variation.