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The role of TPA I/D and PAI-1 4G/5G polymorphisms in multiple sclerosis.
Zivkovic, Maja; Starcevic Cizmarevic, Nada; Lovrecic, Luca; Klupka-Saric, Inge; Stankovic, Aleksandra; Gasparovic, Iva; Lavtar, Polona; Dincic, Evica; Stojkovic, Ljiljana; Rudolf, Gorazd; Jazbec, Sasa Sega; Perkovic, Olivio; Sinanovic, Osman; Sepcic, Juraj; Kapovic, Miljenko; Peterlin, Borut; Ristic, Smiljana.
Afiliación
  • Zivkovic M; Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia.
  • Starcevic Cizmarevic N; Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
  • Lovrecic L; Clinical Institute of Medical Genetics, University Medical Centre, 1000 Ljubljana, Slovenia.
  • Klupka-Saric I; Department of Neurology, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.
  • Stankovic A; Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia.
  • Gasparovic I; Department of Neurology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia.
  • Lavtar P; Clinical Institute of Medical Genetics, University Medical Centre, 1000 Ljubljana, Slovenia.
  • Dincic E; Neurology Clinic, Military Medical Academy, 11000 Belgrade, Serbia.
  • Stojkovic L; Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia.
  • Rudolf G; Clinical Institute of Medical Genetics, University Medical Centre, 1000 Ljubljana, Slovenia.
  • Jazbec SS; Department of Neurology, University Medical Centre, 1000 Ljubljana, Slovenia.
  • Perkovic O; Department of Neurology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia.
  • Sinanovic O; Department of Neurology, School of Medicine, University of Tuzla, 75000 Tuzla, Bosnia and Herzegovina.
  • Sepcic J; Postgraduate Studies, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
  • Kapovic M; Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
  • Peterlin B; Clinical Institute of Medical Genetics, University Medical Centre, 1000 Ljubljana, Slovenia.
  • Ristic S; Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia ; Department of Neurology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia.
Dis Markers ; 2014: 362708, 2014.
Article en En | MEDLINE | ID: mdl-24825926
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activador de Tejido Plasminógeno / Inhibidor 1 de Activador Plasminogénico / Esclerosis Múltiple Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Dis Markers Asunto de la revista: BIOQUIMICA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activador de Tejido Plasminógeno / Inhibidor 1 de Activador Plasminogénico / Esclerosis Múltiple Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Dis Markers Asunto de la revista: BIOQUIMICA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos