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Multiple Sclerosis
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PAI and TPA gene polymorphisms in multiple sclerosis

Luca Lovrecic

Division of Medical Genetics, UMC, Ljubljana, Slovenia

Smiljana Ristic

Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Croatia

Nada Starcevic-Cizmarevic

Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Croatia

Bojana Brajenovic-Milic

Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Croatia

Sasa Sega Jazbec

Department of Neurology, UMC Ljubljana, Slajmerjeva 3, 1000 Ljubljana, Slovenia

Juraj Sepcic

Postgraduate studies, School of Medicine, University of Rijeka, Croatia

Miljenko Kapovic

Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Croatia

Borut Peterlin

Division of Medical Genetics, UMC, Ljubljana, Slovenia, Borut.Peterlin{at}guest.arnes.si

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. Multiple Sclerosis 2008; 14: 243—247. http://msj.sagepub.com

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

This version was published on March 1, 2008

Multiple Sclerosis, Vol. 14, No. 2, 243-247 (2008)
DOI: 10.1177/1352458507082603
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