title: Liver X Receptor Genes Variants Modulate ALS Phenotype.
abstract: Amyotrophic lateral sclerosis (ALS) is one of the most severe motor neuron (MN) disorders in adults. Phenotype of ALS patients is highly variable and may be influenced by modulators of energy metabolism. Recent works have implicated the liver X receptors α and β (LXRs), either in the propagation process of ALS or in the maintenance of MN survival. LXRs are nuclear receptors activated by oxysterols, modulating cholesterol levels, a suspected modulator of ALS severity. In a cohort of 438 ALS patients and 330 healthy controls, the influence of LXR genes on ALS risk and phenotype was studied using single nucleotide polymorphisms (SNPs). The two LXRα SNPs rs2279238 and rs7120118 were shown to be associated with age at onset in ALS patients. Consistently, homozygotes were twice more correlated than were heterozygotes to delayed onset. The onset was thus delayed by 3.9 years for rs2279238 C/T carriers and 7.8 years for T/T carriers. Similar results were obtained for rs7120118 (+2.1 years and +6.7 years for T/C and C/C genotypes, respectively). The LXRβ SNP rs2695121 was also shown to be associated with a 30% increase of ALS duration (p = 0.0055, FDR = 0.044). The tested genotypes were not associated with ALS risk. These findings add further evidence to the suspected implication of LXR genes in the disease process of ALS and might open new perspectives in ALS therapeutics.
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, CHU Nîmes et Université de Montpellier, Nîmes, France. kevin.mouzat@inserm.fr.|INSERM UMR1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi, Montpellier, France. kevin.mouzat@inserm.fr.
authors.forename: Kevin
authors.identifier: http://orcid.org/0000-0003-3832-9883
authors.initials: K
authors.lastname: Mouzat
authors.affiliation: IMAG, UMR 5149, DIM, CHRU de Montpellier, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molinari
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, CHU Nîmes et Université de Montpellier, Nîmes, France.
authors.forename: Jovana
authors.initials: J
authors.lastname: Kantar
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, CHU Nîmes et Université de Montpellier, Nîmes, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Polge
authors.affiliation: Centre SLA, Service de Neurologie et Neurophysiologie Clinique, CHRU de Tours, UMR INSERM U930, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.affiliation: Centre SLA, Service de Neurologie, CHU Limoges, Limoges, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Couratier
authors.affiliation: Centre SLA, Service de Neurologie A, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Clavelou
authors.affiliation: INSERM UMR1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi, Montpellier, France.|ALS Center, Département de Neurologie, CHU Gui de Chauliac, Montpellier, France.
authors.forename: Raul
authors.initials: R
authors.lastname: Juntas-Morales
authors.affiliation: INSERM UMR1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi, Montpellier, France.|ALS Center, Département de Neurologie, CHU Gui de Chauliac, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pageot
authors.affiliation: Génétique Reproduction et Développement, Clermont Université Clermont Université, Clermont-Ferrand, France; CNRS, UMR 6293, GReD, Aubière, France; INSERM, UMR 1103, GReD, Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, Clermont-Ferrand, France.
authors.forename: Jean -Marc A
authors.initials: J-A
authors.lastname: Lobaccaro
authors.affiliation: INSERM UMR1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi, Montpellier, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Raoul
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, CHU Nîmes et Université de Montpellier, Nîmes, France.|INSERM UMR1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi, Montpellier, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Lumbroso
authors.affiliation: INSERM UMR1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi, Montpellier, France.|ALS Center, Département de Neurologie, CHU Gui de Chauliac, Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Camu
mesh_terms: D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D000071518:Liver X Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000071518:Liver X Receptors
keywords: ALS phenotype; Amyotrophic lateral sclerosis; Liver X receptors; Neurodegeneration; Single nucleotide polymorphism