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PAI and TPA gene polymorphisms in multiple sclerosis

¹ Division of Medical Genetics, UMC, Ljubljana, Slovenia
² Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Croatia
³ Department of Neurology, UMC Ljubljana, lajmerjeva 3, 1000 Ljubljana, Slovenia
⁴ Postgraduate studies, School of Medicine, University of Rijeka, Croatia

^* To whom correspondence should be addressed.

	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.

Key Words: gene polymorphism; multiple sclerosis; PAI 4G/5G; TPA Alu I/D; susceptibility gene

First published on November 6, 2007, doi:10.1177/1352458507082603

Multiple Sclerosis 2008;14:243.

A more recent version of this article appeared on March 1, 2008


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