C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position −675 of the PAI-1 gene

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 18; no. 3; pp. 220 - 226
• Main Authors: Testa, R, Bonfigli, A.R, Sirolla, C, Marra, M, Boemi, M, Mari, D, Sacchi, E, Dolci, A, Catalano, A, Procopio, A, Ceriello, A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2008
• Subjects: C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular; Case-Control Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Female; Fibrinolysis; Genotype; Humans; Male; Middle Aged; PAI-1 genotype; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen activator inhibitor type 1; Polymerase Chain Reaction - methods; Polymorphism, Genetic; Promoter Regions, Genetic - genetics; Regression Analysis; Type 2 diabetes; Type 2 diabetes; Plasminogen activator inhibitor type 1; C-reactive protein; Fibrinolysis; PAI-1 genotype
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2006.10.001

Abstract Background and aims C-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. “In vitro” studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications. Methods and results Two hundred and ninety-five type 2 diabetic patients (age 60.9 ± 10.5 years) and 290 healthy controls (age 59.2 ± 11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found ( r = 0.45, p < 0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r = 0.31, p < 0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r = 0.64 p < 0.001) and 4G/5G (partial r = 0.47, p < 0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r = 0.45, p < 0.001) and in 4G/5G (partial r = 0.34, p = 0.007) diabetic patients. Conclusions These findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.