The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis
2014
Аутори
Živković, MajaStarčević Čizmarević, Nada
Lovrečić, Luca
Klupka-Saric, Inge
Stanković, Aleksandra
Gasparovic, Iva
Lavtar, Polona
Dinčić, Evica
Stojković, Ljiljana S.
Rudolf, Gorazd
Jazbec, Sasa Sega
Perkovic, Olivio
Sinanovic, Osman
Sepčić, Juraj
Kapović, Miljenko
Peterlin, Borut
Ristić, Smiljana
Чланак у часопису
Метаподаци
Приказ свих података о документуАпстракт
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 sig...nificant 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.
Извор:
Disease Markers, 2014Финансирање / пројекти:
- Генетска основа хуманих васкуларних и инфламаторних болести (RS-MESTD-Basic Research (BR or ON)-175085)
- University of Rijeka, Republic of Croatia [13.06.1.1.10], National Research Agency of the Republic of Slovenia [J3-3628]
DOI: 10.1155/2014/362708
ISSN: 0278-0240; 1875-8630
WoS: 000334594100001
Scopus: 2-s2.0-84900036954
Колекције
Институција/група
VinčaTY - JOUR AU - Živković, Maja AU - Starčević Čizmarević, Nada AU - Lovrečić, Luca AU - Klupka-Saric, Inge AU - Stanković, Aleksandra AU - Gasparovic, Iva AU - Lavtar, Polona AU - Dinčić, Evica AU - Stojković, Ljiljana S. AU - Rudolf, Gorazd AU - Jazbec, Sasa Sega AU - Perkovic, Olivio AU - Sinanovic, Osman AU - Sepčić, Juraj AU - Kapović, Miljenko AU - Peterlin, Borut AU - Ristić, Smiljana PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5963 AB - 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. T2 - Disease Markers T1 - The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis DO - 10.1155/2014/362708 ER -
@article{ author = "Živković, Maja and Starčević Čizmarević, Nada and Lovrečić, Luca and Klupka-Saric, Inge and Stanković, Aleksandra and Gasparovic, Iva and Lavtar, Polona and Dinčić, Evica and Stojković, Ljiljana S. and Rudolf, Gorazd and Jazbec, Sasa Sega and Perkovic, Olivio and Sinanovic, Osman and Sepčić, Juraj and Kapović, Miljenko and Peterlin, Borut and Ristić, Smiljana", year = "2014", abstract = "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.", journal = "Disease Markers", title = "The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis", doi = "10.1155/2014/362708" }
Živković, M., Starčević Čizmarević, N., Lovrečić, L., Klupka-Saric, I., Stanković, A., Gasparovic, I., Lavtar, P., Dinčić, E., Stojković, L. S., Rudolf, G., Jazbec, S. S., Perkovic, O., Sinanovic, O., Sepčić, J., Kapović, M., Peterlin, B.,& Ristić, S.. (2014). The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis. in Disease Markers. https://doi.org/10.1155/2014/362708
Živković M, Starčević Čizmarević N, Lovrečić L, Klupka-Saric I, Stanković A, Gasparovic I, Lavtar P, Dinčić E, Stojković LS, Rudolf G, Jazbec SS, Perkovic O, Sinanovic O, Sepčić J, Kapović M, Peterlin B, Ristić S. The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis. in Disease Markers. 2014;. doi:10.1155/2014/362708 .
Živković, Maja, Starčević Čizmarević, Nada, Lovrečić, Luca, Klupka-Saric, Inge, Stanković, Aleksandra, Gasparovic, Iva, Lavtar, Polona, Dinčić, Evica, Stojković, Ljiljana S., Rudolf, Gorazd, Jazbec, Sasa Sega, Perkovic, Olivio, Sinanovic, Osman, Sepčić, Juraj, Kapović, Miljenko, Peterlin, Borut, Ristić, Smiljana, "The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis" in Disease Markers (2014), https://doi.org/10.1155/2014/362708 . .