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

• Published in: Disease markers Vol. 2014; no. 2014; pp. 1 - 8
• Main Authors: Klupka-Sarić, Inge, Lovrečić, Luca, Starčević Čizmarević, Nada, Živković, Maja, Stanković, Aleksandra, Gašparović, Iva, Lavtar, Polona, Dinčić, Evica, Stojković, Ljiljana, Rudolf, Gorazd, Šega Jazbec, Saša, Perković, Olivio, Sinanović, Osman, Sepčić, Juraj, Kapović, Miljenko, Peterlin, Borut, Ristić, Smiljana
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2014; Hindawi Publishing Corporation
• Subjects: Case-Control Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; INDEL Mutation; Multiple Sclerosis - genetics; Plasminogen Activator Inhibitor 1 - genetics; Polymorphism, Genetic; Risk Factors; Tissue Plasminogen Activator - genetics
• ISSN: 0278-0240; 1875-8630
• DOI: 10.1155/2014/362708

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, P=0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P=0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P=0.017). 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.