title: A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population.
abstract: Amyotrophic lateral sclerosis is sporadic (SALS) in 90% of cases and has complex environmental and genetic influences. Nogo protein inhibits neurite outgrowth and is overexpressed in muscle in ALS. Our aims were to study the reticulon 4 receptor gene RTN4R which encodes Nogo 1 receptor (NgR1) in SALS, to test if the variants were associated with variable expression of the gene and whether NgR1 protein expression was modified in a transgenic mouse model of ALS. We genotyped three single nucleotide polymorphisms (SNPs; rs701421, rs701427, and rs1567871) of the RTN4R gene in 364 SALS French patients and 430 controls. We examined expression of RTN4R mRNA by quantitative PCR in control post mortem human brain tissue. We determined the expression of NgR1 protein in spinal motor neurons from a SOD1 G86R ALS mouse model. We observed significant associations between SALS and RTN4R alleles. Messenger RNA expression from RTN4R in human cortical brain tissue correlated significantly with the genotypes of rs701427. NgR1 protein expression was reduced in Nogo A positive motor neurons from diseased transgenic animals. In conclusion, these observations suggest that a functional RTN4R gene variant is associated with SALS. This variant may act in concert with other genetic variants or environmental influences.
authors.affiliation: a INSERM U930 , Tours , France.|b Université François Rabelais , Tours , France.
authors.forename: Maïté
authors.initials: M
authors.lastname: Amy
authors.affiliation: c Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Staehlin
authors.affiliation: d INSERM U1118, Mécanismes Centraux et Périphériques de la Neurodégénérescence , Strasbourg , France.|e Université de Strasbourg, UMRS 1118 , Strasbourg , France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: René
authors.affiliation: a INSERM U930 , Tours , France.|b Université François Rabelais , Tours , France.|f Service de Biochimie et Biologie Moléculaire, Hôpital Bretonneau , CHRU de Tours, Tours , France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.affiliation: a INSERM U930 , Tours , France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Marouillat
authors.affiliation: a INSERM U930 , Tours , France.
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.affiliation: a INSERM U930 , Tours , France.|b Université François Rabelais , Tours , France.|f Service de Biochimie et Biologie Moléculaire, Hôpital Bretonneau , CHRU de Tours, Tours , France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.affiliation: g Northern Navajo Medical Center , Shiprock NM , USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gordon
authors.affiliation: h ALS Centre, Hôpital Gui de Chauliac, CHU de Montpellier , Montpellier , France.
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.affiliation: a INSERM U930 , Tours , France.|b Université François Rabelais , Tours , France.|i ALS Centre, Department of Neurology , CHRU de Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.affiliation: d INSERM U1118, Mécanismes Centraux et Périphériques de la Neurodégénérescence , Strasbourg , France.|e Université de Strasbourg, UMRS 1118 , Strasbourg , France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
authors.affiliation: j Laboratory of Neuromorphology, Semmelweis University and the Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.affiliation: c Institute of Psychopharmacology at Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg , Mannheim , Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Sommer
authors.affiliation: a INSERM U930 , Tours , France.|b Université François Rabelais , Tours , France.|f Service de Biochimie et Biologie Moléculaire, Hôpital Bretonneau , CHRU de Tours, Tours , France.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D005602:France; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism; D000070816:Nogo Receptor 1; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D044465:White People / Q000235:genetics*
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D012333:RNA, Messenger; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Nogo-66 receptor; SNP; association study; gene expression; motor neurons; reticulon 4 receptor gene (RTN4R); sporadic amyotrophic lateral sclerosis