A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population

• Verfasst von: Amy, Maïté [VerfasserIn]
• Verfasst von: Sommer, Wolfgang H. [VerfasserIn]
• Titel: A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population
• Verf.angabe: Maïté Amy, Oliver Staehlin, Frédérique René, Hélène Blasco, Sylviane Marouillat, Hussein Daoud, Patrick Vourc’h, Paul H. Gordon, William Camu, Philippe Corcia, Jean-Philippe Loeffler, Miklós Palkovits, Wolfgang H. Sommer and Christian R. Andres
• E-Jahr: 2015
• Jahr: 17 Jun 2015
• Umfang: 7 S.
• Fussnoten: Gesehen am 14.12.2017
• Titel Quelle: Enthalten in: Amyotrophic lateral sclerosis & frontotemporal degeneration
• Ort Quelle: Abingdon : Taylor Francis Group, 2013
• Jahr Quelle: 2015
• Band/Heft Quelle: 16(2015), 7-8, Seite 490-496
• ISSN Quelle: 2167-9223
• DOI: doi:10.3109/21678421.2015.1051988
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: association study
• Sach-SW: gene expression
• Sach-SW: motor neurons
• Sach-SW: Nogo-66 receptor
• Sach-SW: reticulon 4 receptor gene (RTN4R)
• Sach-SW: SNP
• Sach-SW: sporadic amyotrophic lateral sclerosis
• K10plus-PPN: 1566379962

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.