Author/Editor		Lovrečić, Luca; Ristić, Smiljana; Starčević-Čizmarević, Nada; Brajenović-Milić, Bojana; Šega-Jazbec, Saša; Sepčić, Juraj; Kapović, Miljenko; Peterlin, Borut
Title		PAI and TPA gene polymorphisms in multiple sclerosis
Type		članek
Source		Mult Scler
Vol. and No.		Letnik 14, št. 2
Publication year		2008
Volume		str. 243-7
Language		eng
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.
Descriptors		ADULT AGED PLASMINOGEN ACTIVATOR INHIBITOR 1 RISK FACTORS