title: Manganese-containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease.
abstract: An alanin-9valin (Ala-9Val) polymorphism in the mitochondrial targeting sequence of manganese-containing superoxide dismutase (Mn-SOD) has recently been described. We studied this polymorphism in 72 Swedish patients with sporadic motor neuron diseases (MND) and controls using an oligonucleotide ligation assay. There were significant differences in genotype between MND patients and controls (P = 0.025), and between male and female MND patients (P = 0.009). Individuals homozygous for the Ala allele had a higher risk for MND [odds ratio, 2.9; 95% confidence interval (CI), 1.3-6.6], which was increased when including only females in the analysis (odds ratio, 5.0; 95% CI, 1.8-14.0). In classical amyotrophic lateral sclerosis, the odds ratio was 3.8 (95% CI, 1.3-10.0), and 5. 5 (95% CI, 1.5-19.9) when including only females. The results suggest that mutations influencing the cellular allocation of Mn-SOD may be a risk factor in MND, especially in females, and that MND may be a disease of misdistribution of the superoxide dismutase enzymes.
authors.affiliation: Departments of Medical Genetics, Umeå University, Umeå, Sweden.
authors.forename: G F
authors.initials: GF
authors.lastname: Van Landeghem
authors.forename: P
authors.initials: P
authors.lastname: Tabatabaie
authors.forename: G
authors.initials: G
authors.lastname: Beckman
authors.forename: L
authors.initials: L
authors.lastname: Beckman
authors.forename: P M
authors.initials: PM
authors.lastname: Andersen
mesh_terms: D000409:Alanine / Q000235:genetics; D000483:Alleles; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D016472:Motor Neuron Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D021382:Protein Sorting Signals; D013482:Superoxide Dismutase; D014633:Valine; D000409:Alanine