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Disease Markers
Volume 2014, Article ID 362708, 8 pages
Research Article

The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

1Laboratory for Radiobiology and Molecular Genetics, “Vinča” Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia
2Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia
3Clinical Institute of Medical Genetics, University Medical Centre, 1000 Ljubljana, Slovenia
4Department of Neurology, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina
5Department of Neurology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia
6Neurology Clinic, Military Medical Academy, 11000 Belgrade, Serbia
7Department of Neurology, University Medical Centre, 1000 Ljubljana, Slovenia
8Department of Neurology, School of Medicine, University of Tuzla, 75000 Tuzla, Bosnia and Herzegovina
9Postgraduate Studies, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia

Received 4 February 2014; Accepted 31 March 2014; Published 16 April 2014

Academic Editor: Ralf Lichtinghagen

Copyright © 2014 Maja Živković et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, ) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, ). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, ). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS.