title: No evidence for genetic association between glutamate transporter EAAT2 and Devic's neuromyelitis optica in caucasians and afro-caribbeans.
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.
authors: Caen University Hospital, Department of Biochemistry, Caen F-14000, France. Electronic address: vincent.hanoux@unicaen.fr.
authors: Vincent
authors: V
authors: Hanoux
authors: Caen University Hospital, Department of Biochemistry, Caen F-14000, France; Université de Caen Basse-Normandie, Medical School, Caen F-14000, France. Electronic address: coulbault-l@chu-caen.fr.
authors: Laurent
authors: L
authors: Coulbault
authors: Caen University Hospital, Department of Neurology, Caen F-14000, France; INSERM U1077 and Ecole Pratique des Hautes Etudes, UMR-S1077, Caen F-14000, France. Electronic address: derache-n@chu-caen.fr.
authors: Nathalie
authors: N
authors: Derache
authors: Fort de France University Hospital, Department of Neurology, Fort de France, F-97261 Martinique, France. Electronic address: philippe.cabre@chu-fortdefrance.fr.
authors: Philippe
authors: P
authors: Cabre
authors: Strasbourg University Hospital, Department of Neurology, Strasbourg F-67085, France. Electronic address: jerome.de.seze@chru-strasbourg.fr.
authors: Jérôme
authors: J
authors: De Seze
authors: 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. Electronic address: romain.marignier@chu-lyon.fr.
authors: Romain
authors: R
authors: Marignier
authors: Strasbourg University Hospital, Department of Neurology, Strasbourg F-67085, France. Electronic address: Gabrielle.Rudolf@chru-strasbourg.fr.
authors: Gabrielle
authors: G
authors: Rudolf
authors: Caen University Hospital, Department of Biostatistics and Clinical Research, Caen F-14000, France. Electronic address: dugue-a@chu-caen.fr.
authors: Audrey
authors: A
authors: Emmanuelle Dugué
authors: Caen University Hospital, Department of Biochemistry, Caen F-14000, France; Université de Caen Basse-Normandie, Medical School, Caen F-14000, France. Electronic address: allouche-s@chu-caen.fr.
authors: Stéphane
authors: S
authors: Allouche
authors: 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.. Electronic address: defer-gi@chu-caen.fr.
authors: Gilles
authors: G
authors: Defer
keywords: Devic's neuromyelitis optica; Excitatory amino acid transporter 2; Genetic association study; Glutamate excitotoxicity; Glutamate transporter; Single nucleotide polymorphisms