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NRAMP1 Polymorphism and Viral Factors in Sardinian Multiple Sclerosis Patients

Published online by Cambridge University Press:  02 December 2014

Maria Gazouli ,
Leonardo Sechi ,
Daniela Paccagnini ,
Stefano Sotgiu ,
Giannina Arru ,
George Nasioulas  and
Dimitrios Vassilopoulos
Maria Gazouli*
Affiliation:
Department of Neurology, School of Medicine, University of Athens, Athens, Greece
Leonardo Sechi
Affiliation:
Dipartimento di Scienze Biomediche, Sezione di Microbiologia Sperimentale e Clinica, Università degli Studi di Sassari, Sassari, Italy
Daniela Paccagnini
Affiliation:
Dipartimento di Scienze Biomediche, Sezione di Microbiologia Sperimentale e Clinica, Università degli Studi di Sassari, Sassari, Italy
Stefano Sotgiu
Affiliation:
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Giannina Arru
Affiliation:
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
George Nasioulas
Affiliation:
Molecular Biology Research Center HYGEIA “Antonis Papayiannis”, Athens, Greece
Dimitrios Vassilopoulos
Affiliation:
Department of Neurology, School of Medicine, University of Athens, Athens, Greece
*
School of Medicine, University of Athens, Michalakopoulou 176, 11527 Goudi, Athens, Greece.
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Abstract

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Background:

Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.

Methods:

Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.

Results:

Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.

Conclusion:

The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

Résumé:

RÉSUMÉ:Contexte:

La sclérose en plaques (SEP) est considérée comme une maladie autoimmune qui survient chez des individus qui y sont prédisposés génétiquement, après une exposition environnementale particulière telle une infection virale. Des études récentes suggèrent qu’il existe une association significative entre la SEP et le polymorphisme fonctionnel 5’–(GT)n situé dans le promoteur du gène NRAMP1. Notre but était d’évaluer la contribution de la variation allélique dans le promoteur du gène NRAMP1 à la susceptibilité à la SEP et d’étudier le rôle de l’infection virale en relation à des génotypes NRAMP1 spécifiques dans une cohorte de Sardes.

Méthodes:

Soixante patients atteints de SEP et 66 volontaires sains ont été génotypés et on a également recherché la présence de séquences de l’EBV et du JCV.

Résultats:

Tel que démontré dans des études antérieures sur les maladies autoimmunes, l’allèle 3 du polymorphisme de répétitions situé dans la région fonctionnelle 5’ (GT)n du promoteur était significativement surexprimé chez les patients atteints de SEP par rapport aux témoins (p = 0,02). Des séquences de l’EBV et du JCV ont été détectées respectivement chez 8 (13,33%) et chez 4 (6,66%) des 60 patients atteints de SEP et chez 5 (7,57%) et 0 des 66 témoins.

Conclusion:

La variation allélique située dans le promoteur de NRAMP1 pourrait contribuer à la prédisposition à la SEP chez les Sardes. Nous n’avons pas confirmé l’association de séquences virales à un génotype NRAMP1 spécifique.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 35 , Issue 4 , September 2008 , pp. 491 - 494
Copyright
Copyright © The Canadian Journal of Neurological 2008

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