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Research Article| Volume 3, ISSUE 1, P89-93, January 2014

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No evidence for genetic association between glutamate transporter EAAT2 and Devic's neuromyelitis optica in caucasians and afro-caribbeans

  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    Vincent Hanoux
    Footnotes
    1 These authors contributed equally to the manuscript.
    Affiliations
    Caen University Hospital, Department of Biochemistry, Caen F-14000, France
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  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    Laurent Coulbault
    Correspondence
    Correspondence to: Caen University Hospital, Department of Biochemistry, avenue de côte de nacre, F-14033 Caen cedex, France. Tel.: +33 231063242; fax: +33 231065172.
    Footnotes
    1 These authors contributed equally to the manuscript.
    Affiliations
    Caen University Hospital, Department of Biochemistry, Caen F-14000, France

    Université de Caen Basse-Normandie, Medical School, Caen F-14000, France
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  • Nathalie Derache
    Affiliations
    Caen University Hospital, Department of Neurology, Caen F-14000, France

    INSERM U1077 and Ecole Pratique des Hautes Etudes, UMR-S1077, Caen F-14000, France
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  • Philippe Cabre
    Affiliations
    Fort de France University Hospital, Department of Neurology, Fort de France, F-97261 Martinique, France
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  • Jérôme De Seze
    Affiliations
    Strasbourg University Hospital, Department of Neurology, Strasbourg F-67085, France
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  • Romain Marignier
    Affiliations
    Hospices Civils de Lyon, Department of Neurology and EDMUS Coordinating Center, Lyon F-69677, France

    INSERM U1028, Lyon Neuroscience Research Center, Neuro-Inflammation and Neuro-Oncology Team, Lyon F-69000, France
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  • Gabrielle Rudolf
    Affiliations
    Strasbourg University Hospital, Department of Neurology, Strasbourg F-67085, France
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  • Audrey Emmanuelle Dugué
    Affiliations
    Caen University Hospital, Department of Biostatistics and Clinical Research, Caen F-14000, France
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  • Stéphane Allouche
    Affiliations
    Caen University Hospital, Department of Biochemistry, Caen F-14000, France

    Université de Caen Basse-Normandie, Medical School, Caen F-14000, France
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  • Gilles Defer
    Affiliations
    Caen University Hospital, Department of Neurology, Caen F-14000, France

    INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP Cyceron, Université de Caen Basse-Normandie, Caen F-14000, France.
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  • On behalf of the NOMADMUS Study Group
    Author Footnotes
    2 NOMADMUS Study Group members for 2010 is as follows: Bertrand Audoin, MD, Ph.D.; David Brassat, MD, Ph.D.; Bruno Brochet, MD, Ph.D.; Philippe Cabre, MD, Ph.D.; Jean-Philippe Camdessanche, MD; William Camu, MD, Ph.D.; Olivier Casez, MD; Giovanni Castelnovo, MD; Michel Clanet, MD, Ph.D.; Pierre Clavelou, MD, Ph.D.; Nicolas Collongues, MD; Christian Confavreux, MD, Ph.D.;François Cotton, MD, Ph.D.; Alain Creange, MD, Ph.D.; Gilles Defer, MD, Ph.D.; Jérôme de Seze, MD, Ph.D.; Marc Debouverie, MD, Ph.D.; Gilles Edan, MD, Ph.D.; Olivier Gout, MD; Guillemette Jousserand, MD; Philippe Kirschen, MD; Pierre Labauge, MD, Ph.D.; Christine Lebrun-Frenay, MD; David Laplaud, MD; Romain Marignier, MD; Thibault Moreau, MD, Ph.D.; Caroline Papeix, MD; Jean Pelletier, MD, Ph.D.; Lucien Rumbach, MD, Ph.D.; Bruno Stankoff, MD, Ph.D.; Ayman Tourbah, MD, Ph.D.; Patrick Vermersch, MD, Ph.D.; Sandra Vukusic, MD, Ph.D.; and Hélène Zéphir, MD. CF-SEP MD Coordinators: Anne Olivier, MD; Bertrand Audoin, MD, Ph.D.; Florent Borgel, MD; David Brassat, MD, Ph.D.; Bruno Brochet, MD, Ph.D.; Philippe Cabre, MD, Ph.D.; William Camu, MD, Ph.D.; Pierre Clavelou, MD, Ph.D.; Alain Créange, MD, Ph.D.; Marc Coustans, MD, Ph.D.; Marc Debouverie, MD, Ph.D.; Gilles Defer, MD, Ph.D.; Jérôme de Seze, MD, Ph.D.; Olivier Gout, MD; Jérôme Grimaud, MD, Ph.D.; Patrick Hautecoeur, MD; Olivier Heinzlef, MD; Pierre Labauge, MD, Ph.D.; David Laplaud, MD; Christine Lebrun-Frenay, MD; Emmanuelle le Page, MD; Claude Mekies, MD; Thibault Moreau, MD, Ph.D.; Caroline Papeix, MD; Jean Pelletier, MD, Ph.D.; Sophie Pittion, MD; Lucien Rumbach, MD; Pierrette Seeldrayers, MD; Ilham Slassi, MD, Ph.D.; Bruno Stankoff, MD, Ph.D.; Ayman Tourbah, MD, Ph.D.; Patrick Vermersch, MD, Ph.D.; Sandra Vukusic, MD, Ph.D.; Sandrine Wiertlevski, MD; and Hélène Zéphir, MD.
  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    2 NOMADMUS Study Group members for 2010 is as follows: Bertrand Audoin, MD, Ph.D.; David Brassat, MD, Ph.D.; Bruno Brochet, MD, Ph.D.; Philippe Cabre, MD, Ph.D.; Jean-Philippe Camdessanche, MD; William Camu, MD, Ph.D.; Olivier Casez, MD; Giovanni Castelnovo, MD; Michel Clanet, MD, Ph.D.; Pierre Clavelou, MD, Ph.D.; Nicolas Collongues, MD; Christian Confavreux, MD, Ph.D.;François Cotton, MD, Ph.D.; Alain Creange, MD, Ph.D.; Gilles Defer, MD, Ph.D.; Jérôme de Seze, MD, Ph.D.; Marc Debouverie, MD, Ph.D.; Gilles Edan, MD, Ph.D.; Olivier Gout, MD; Guillemette Jousserand, MD; Philippe Kirschen, MD; Pierre Labauge, MD, Ph.D.; Christine Lebrun-Frenay, MD; David Laplaud, MD; Romain Marignier, MD; Thibault Moreau, MD, Ph.D.; Caroline Papeix, MD; Jean Pelletier, MD, Ph.D.; Lucien Rumbach, MD, Ph.D.; Bruno Stankoff, MD, Ph.D.; Ayman Tourbah, MD, Ph.D.; Patrick Vermersch, MD, Ph.D.; Sandra Vukusic, MD, Ph.D.; and Hélène Zéphir, MD. CF-SEP MD Coordinators: Anne Olivier, MD; Bertrand Audoin, MD, Ph.D.; Florent Borgel, MD; David Brassat, MD, Ph.D.; Bruno Brochet, MD, Ph.D.; Philippe Cabre, MD, Ph.D.; William Camu, MD, Ph.D.; Pierre Clavelou, MD, Ph.D.; Alain Créange, MD, Ph.D.; Marc Coustans, MD, Ph.D.; Marc Debouverie, MD, Ph.D.; Gilles Defer, MD, Ph.D.; Jérôme de Seze, MD, Ph.D.; Olivier Gout, MD; Jérôme Grimaud, MD, Ph.D.; Patrick Hautecoeur, MD; Olivier Heinzlef, MD; Pierre Labauge, MD, Ph.D.; David Laplaud, MD; Christine Lebrun-Frenay, MD; Emmanuelle le Page, MD; Claude Mekies, MD; Thibault Moreau, MD, Ph.D.; Caroline Papeix, MD; Jean Pelletier, MD, Ph.D.; Sophie Pittion, MD; Lucien Rumbach, MD; Pierrette Seeldrayers, MD; Ilham Slassi, MD, Ph.D.; Bruno Stankoff, MD, Ph.D.; Ayman Tourbah, MD, Ph.D.; Patrick Vermersch, MD, Ph.D.; Sandra Vukusic, MD, Ph.D.; Sandrine Wiertlevski, MD; and Hélène Zéphir, MD.

      Highlights

      • We studied EAAT2 genetic variations in patients presenting with Devic's disease.
      • Whole coding region and consensus sequences flanking each exon were sequenced.
      • No novel mutations or polymorphisms were found in EAAT2 gene.
      • No association was found between EAAT2 gene and Devic's disease.

      Abstract

      Devic's neuromyelitis optica (NMO) is a severe inflammatory and autoimmune disease producing demyelinating lesions. Recent data suggest that a complex genetic component could be involved. While impairment of glutamate homeostasis has emerged as a contributing etiological factor in NMO, a genetic alteration of Excitatory Amino Acid Transporter 2 (EAAT2/SLC1A2), the major glutamate transporter in the Central Nervous System (CNS), could contribute to glutamate excitotoxicity and then must be considered.
      We evaluated whether mutations and/or single nucleotide polymorphisms (SNPs) in EAAT2 gene, are associated with susceptibility to NMO. We studied a cohort of NMO sporadic cases including afro-caribbean patients (n=81; French cohort of Devic's neuromyelitis optica—NOMADMUS cohort) and compared to control subjects (n=56). We sequenced the whole coding region of EAAT2 gene and splicing consensus sequences flanking each exon. The results obtained from all NMO samples did not show any novel mutations and/or SNPs both in the coding region and splicing sites of EAAT2 gene compared to controls subjects. We reported three synonymous SNPs (rs752949, rs1042113 and rs7102949) but only rs7102949 was found in afro-caribbean. Genotype frequencies did not differ between patients and controls for the three SNPs in caucasians and afro-caribbeans (rs752949: p=0.71 and p=0.37, respectively; rs1042113: p=0.73 and p=0.35, respectively; rs7102949: p=0.08 in afro-caribbeans). Our data showed no evidence for a genetic association between EAAT2 gene and Devic's neuromyelitis optica.

      Keywords

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