title: PAI and TPA gene polymorphisms in multiple sclerosis.
abstract: Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. It manifests as acute focal inflammatory demyelination and axonal loss with limited remyelination and results in the chronic multifocal sclerotic plaques. Previously published data showed impaired fibrinolysis in MS. Tissue plasminogen activator t-PA is a serine protease that catalyses the activation of plasmin, which mediates the effects of fibrinolytic system. Alu insertion/deletion (I/D) genetic polymorphism in TPA gene in MS patients has not been analysed previously. The major inhibitor of t-PA is plasminogen activator inhibitor-1 (PAI-1). Its gene expression is modulated by functional genetic polymorphism in the promoter (4G/5G). In the present study, an association of two genetic polymorphisms with MS, its progression and subtype were analysed. TPA DD/PAI-1 4G4G genotype combination has reached a borderline significance for reduced risk for MS (OR = 0.543, 95% CI 0.301-0.978, P = 0.04), suggesting a gene-gene interaction. The explanation for this interaction may be a complex interplay between these two pleiotropic proteins within the brain tissue and in plasma.
authors.affiliation: Division of Medical Genetics, UMC, Ljubljana, Slovenia.
authors.forename: Luca
authors.initials: L
authors.lastname: Lovrecic
authors.forename: Smiljana
authors.initials: S
authors.lastname: Ristić
authors.forename: Nada
authors.initials: N
authors.lastname: Starcević-Cizmarević
authors.forename: Bojana
authors.initials: B
authors.lastname: Brajenović-Milić
authors.forename: Sasa Sega
authors.initials: SS
authors.lastname: Jazbec
authors.forename: Juraj
authors.initials: J
authors.lastname: Sepcić
authors.forename: Miljenko
authors.initials: M
authors.lastname: Kapović
authors.forename: Borut
authors.initials: B
authors.lastname: Peterlin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000276:immunology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator