mtDNA nt13708A variant increases the risk of multiple sclerosis

Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility. In order to investigate the role of mtDNA variations in MS, we investigated six European MS case-control cohorts comprising >5,000 individual...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2008-02, Vol.3 (2), p.e1530-e1530
Main Authors: Yu, Xinhua, Koczan, Dirk, Sulonen, Anna-Maija, Akkad, Denis A, Kroner, Antje, Comabella, Manuel, Costa, Gianna, Corongiu, Daniela, Goertsches, Robert, Camina-Tato, Montserrat, Thiesen, Hans-Juergen, Nyland, Harald I, Mørk, Sverre J, Montalban, Xavier, Rieckmann, Peter, Marrosu, Maria G, Myhr, Kjell-Morten, Epplen, Joerg T, Saarela, Janna, Ibrahim, Saleh M
Format: Article
Language:English
Subjects:
Alleles
Case-Control Studies
Chromosomes
Clinical medicine
Deoxyribonucleic acid
Disease
DNA
DNA, Mitochondrial - genetics
Electron Transport Complex I - genetics
Europe - epidemiology
Gene Frequency
Genetic aspects
Genetic Predisposition to Disease
Genetics
Genetics and Genomics/Genetics of Disease
Genomes
Genomics
Haplotypes
Hospitals
Humans
Immunology
Immunology/Autoimmunity
Laboratories
Medicine
Metabolism
Mitochondrial DNA
Mitochondrial Proteins - genetics
Molecular Epidemiology
Multiple sclerosis
Multiple Sclerosis - epidemiology
Multiple Sclerosis - etiology
Multiple Sclerosis - genetics
Mutation
Neurology
Neurosciences
Odds Ratio
Pathogenesis
Polymorphism
Polymorphism, Single Nucleotide - physiology
Population structure
Proteins
Public health
Sequence Analysis, DNA
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Studies
Type 2 diabetes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0001530