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

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.