Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis
pmid: 21276595
Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis
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).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.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.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.
Male, Kaplan-Meier Estimate, MESH: Genotype, Cohort Studies, Gene Frequency, MESH: Reverse Transcriptase Polymerase Chain Reaction, 80 and over, Age of Onset, MESH: Cohort Studies, Cation Transport Proteins, MESH: Amyotrophic Lateral Sclerosis, MESH: Aged, Aged, 80 and over, MESH: Iron, MESH: Middle Aged, MESH: DNA, Middle Aged, MESH: Case-Control Studies, MESH: Young Adult, Female, Adult, MESH: Mutation, Adolescent, Genotype, MESH: Age of Onset, Iron, 610, MESH: Multivariate Analysis, MESH: Cation Transport Proteins, MESH: Gene Frequency, Humans, MESH: Kaplan-Meier Estimate, Alleles, Aged, MESH: Adolescent, MESH: Humans, MESH: Alleles, Amyotrophic Lateral Sclerosis, MESH: Adult, DNA, MESH: Male, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Multivariate Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Male, Kaplan-Meier Estimate, MESH: Genotype, Cohort Studies, Gene Frequency, MESH: Reverse Transcriptase Polymerase Chain Reaction, 80 and over, Age of Onset, MESH: Cohort Studies, Cation Transport Proteins, MESH: Amyotrophic Lateral Sclerosis, MESH: Aged, Aged, 80 and over, MESH: Iron, MESH: Middle Aged, MESH: DNA, Middle Aged, MESH: Case-Control Studies, MESH: Young Adult, Female, Adult, MESH: Mutation, Adolescent, Genotype, MESH: Age of Onset, Iron, 610, MESH: Multivariate Analysis, MESH: Cation Transport Proteins, MESH: Gene Frequency, Humans, MESH: Kaplan-Meier Estimate, Alleles, Aged, MESH: Adolescent, MESH: Humans, MESH: Alleles, Amyotrophic Lateral Sclerosis, MESH: Adult, DNA, MESH: Male, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Multivariate Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
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