engleski

Plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism and its role in the progression of multiple sclerosis

Our aim was to test the hypothesis that impaired proteolytic mechanisms in multiple sclerosis (MS), which were previously published to play a role in the evolution of MS, were in part due to the common functional genetic polymorphism in the plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G. Previously reported data showed defective fibrinolysis in MS with PAI-1 being one of the major enzymes included. The effects of fibrinolytic system are mediated by plasmin, the protease generated by the action of plasminogen activators (PA) on the inactive precursor plasminogen. The major inhibitor of tissue PA is PAI-1. The genetic polymorphism 4G/5G modulates the expression of PAI-1 gene and individuals with the 4G/4G genotype have increased plasma PAI-1 concentrations. PAI-1 4G/5G polymorphism was evaluated in the group of 313 patients with multiple sclerosis (MS) and 376 healthy controls from Slovenia and Croatia. The significance of the difference of observed alleles and genotypes were determined using the χ2 test. Relationship of the genotypes and the disease progression and the age of onset of the disease was tested by one–way ANOVA test and logistic regression analysis. Our results showed statistically significant differences in the distribution of PAI 4G/5G genotypes with respect to progression of the disease: ANOVA (P<0.01) and logistic regression (P<0.02) analysis. Namely, genotype 5G5G was associated with lower progression index PI, which was calculated as a ratio EDSS/disease duration in years. Our results suggest that reduced capacity for proteinase inhibition may be involved in the slower progression of MS.

: multiple sclerosis; Plasminogen activator inhibitor 1 gene; PAI-1

nije evidentirano