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

Autor: Aleksandra Stanković, Osman Sinanović, Iva Gašparović, Olivio Perković, Gorazd Rudolf, Smiljana Ristić, Miljenko Kapović, Nada Starčević Čizmarević, Saša Šega Jazbec, Polona Lavtar, Maja Živković, Ljiljana Stojković, Luca Lovrečić, Juraj Sepčić, Inge Klupka-Sarić, Evica Dinčić, Borut Peterlin
Rok vydání: 2014
Předmět:
Multiple Sclerosis
Article Subject
NDEL Mutation Multiple Sclerosis/genetics
medicine.medical_treatment
Clinical Biochemistry
Tissue Plasminogen Activator/genetics
Biology
chemistry.chemical_compound
BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Genetics
Genomics and Proteomics
Gene Frequency
INDEL Mutation
Risk Factors
BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Neurology
Plasminogen Activator Inhibitor 1
Fibrinolysis
Genotype
Genetics
medicine
Humans
Plasminogen Activator Inhibitor 1/genetics
Genetic Predisposition to Disease
Molecular Biology
Allele frequency
Genetic Association Studies
Multiple sclerosis
TPA Alu I/D
PAI 4G/5G
Gene polymorphism
Susceptibility gene
lcsh:R5-920
Polymorphism
Genetic
Biochemistry (medical)
Proteolytic enzymes
BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Neurologija
General Medicine
medicine.disease
Molecular biology
3. Good health
Humans I
chemistry
Case-Control Studies
Tissue Plasminogen Activator
Plasminogen activator inhibitor-1
Immunology
lcsh:Medicine (General)
BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Genetika
genomika i proteomika čovjeka
Plasminogen activator
Research Article
Zdroj: Disease Markers
Volume 2014
Disease Markers, Vol 2014 (2014)
ISSN: 1875-8630
0278-0240
DOI: 10.1155/2014/362708
Popis: 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.
Databáze: OpenAIRE
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