title: mtDNA nt13708A variant increases the risk of multiple sclerosis.
abstract: BACKGROUND
  Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility.
  
  
  RESULTS
  In order to investigate the role of mtDNA variations in MS, we investigated six European MS case-control cohorts comprising >5,000 individuals. Three well matched cohorts were genotyped with seven common, potentially functional mtDNA single nucleotide polymorphisms (SNPs). A SNP, nt13708 G/A, was significantly associated with MS susceptibility in all three cohorts. The nt13708A allele was associated with an increased risk of MS (OR = 1.71, 95% CI 1.28-2.26, P = 0.0002). Subsequent sequencing of the mtDNA of 50 individuals revealed that the nt13708 itself, rather than SNPs linked to it, was responsible for the association. However, the association of nt13708 G/A with MS was not significant in MS cohorts which were not well case-control matched, indicating that the significance of association was affected by the population structure of controls.
  
  
  CONCLUSIONS
  Taken together, our finding identified the nt13708A variant as a susceptibility allele to MS, which could contribute to defining the role of the mitochondrial genome in MS pathogenesis.
authors.affiliation: Section of Immunogenetics, University of Rostock, Rostock, Germany.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yu
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Sulonen
authors.forename: Denis A
authors.initials: DA
authors.lastname: Akkad
authors.forename: Antje
authors.initials: A
authors.lastname: Kroner
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.forename: Gianna
authors.initials: G
authors.lastname: Costa
authors.forename: Daniela
authors.initials: D
authors.lastname: Corongiu
authors.forename: Robert
authors.initials: R
authors.lastname: Goertsches
authors.forename: Montserrat
authors.initials: M
authors.lastname: Camina-Tato
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Thiesen
authors.forename: Harald I
authors.initials: HI
authors.lastname: Nyland
authors.forename: Sverre J
authors.initials: SJ
authors.lastname: Mørk
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Peter
authors.initials: P
authors.lastname: Rieckmann
authors.forename: Maria G
authors.initials: MG
authors.lastname: Marrosu
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.forename: Joerg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Janna
authors.initials: J
authors.lastname: Saarela
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D017720:Molecular Epidemiology; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I