title: Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis.
abstract: BACKGROUND
  Dysregulation of iron homeostasis is one possible pathophysiological mechanism involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). SLC11A2 gene encodes the divalent metal transport 1 (DMT1) mediating iron transport in cerebral endosomal compartments. The objective of the study was to analyze DMT1 as a possible risk or modulating factor in sporadic ALS (SALS).
  
  
  METHODS
  We performed a case-control association study on an intronic polymorphism (rs407135) previously analyzed in another neurodegenerative disease, Alzheimer's disease. This polymorphism was studied by DNA sequencing in 579 French patients with SALS and 517 healthy matched individuals. The clinical characteristics of patients were analyzed in relation to their genotypes.
  
  
  RESULTS
  We observed that the C allele of rs407135 in SLC11A2 was associated with a shorter disease duration in SALS patients with onset in the legs [Hazard ratio: 1.5 [1.1-2.1] (p=0.02)]. These results are in line with previous observations suggesting that bulbar and spinal motor neurons have different metabolic regulation and gene expression profiles.
  
  
  CONCLUSIONS
  Our findings support an implication for iron metabolism in ALS and suggest that the genotype of the SLC11A2 gene could modulate the duration of the disease in French SALS patients.
authors.affiliation: UMR INSERM U930-CNRS 2448, Université François-Rabelais de Tours, Tours, France. helene.blasco@univ-tours.fr
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.forename: Yann
authors.initials: Y
authors.lastname: Nadjar
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Ribourtout
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gordon
authors.forename: Yves-Olivier
authors.initials: YO
authors.lastname: Guettard
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.forename: Julien
authors.initials: J
authors.lastname: Praline
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007501:Iron / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D004247:DNA; D007501:Iron; D000099236:Solute Carrier Family 11, Member 2