1. mtDNA nt13708A Variant Increases the Risk of Multiple Sclerosis.
- Author
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Xinhua Yu, 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, and Ibrahim, Saleh M.
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MITOCHONDRIAL DNA , *GENETIC polymorphisms , *MULTIPLE sclerosis , *NUCLEOTIDES , *DISEASE progression , *DISEASE susceptibility , *NUCLEOTIDE sequence , *MEDICAL research - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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