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.
OBJECTIVE
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.


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.
Testa
R
R
Department of Gerontological Research, Diabetology Unit, INRCA Hospital, Via della Montagnola 81, I-60131 Ancona, Italy. r.testa@inrca.it
Bonfigli
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AR
Sirolla
C
C
Marra
M
M
Boemi
M
M
Mari
D
D
Sacchi
E
E
Dolci
A
A
Catalano
A
A
Procopio
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Ceriello
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A
D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012044:Regression Analysis
D017395:Plasminogen Activator Inhibitor 1; D002097:C-Reactive Protein