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mtDNA nt13708A variant increases the risk of multiple sclerosis. PLoS One 2008 Feb 13;3(2):e1530



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Scopus ID

2-s2.0-45349109162 (requires institutional sign-in at Scopus site)   66 Citations


BACKGROUND: Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility.

METHODS AND FINDINGS: 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.

Author List

Yu X, Koczan D, Sulonen AM, Akkad DA, Kroner A, Comabella M, Costa G, Corongiu D, Goertsches R, Camina-Tato M, Thiesen HJ, Nyland HI, Mørk SJ, Montalban X, Rieckmann P, Marrosu MG, Myhr KM, Epplen JT, Saarela J, Ibrahim SM


Antje Kroner-Milsch MD, PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Case-Control Studies
DNA, Mitochondrial
Electron Transport Complex I
Gene Frequency
Genetic Predisposition to Disease
Mitochondrial Proteins
Molecular Epidemiology
Multiple Sclerosis
Odds Ratio
Polymorphism, Single Nucleotide
Sequence Analysis, DNA