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. 2008 Feb 13;3(2):e1530.
doi: 10.1371/journal.pone.0001530.

mtDNA nt13708A variant increases the risk of multiple sclerosis

Xinhua Yu  1 , Dirk Koczan, Anna-Maija Sulonen, Denis A Akkad, Antje Kroner, Manuel Comabella, Gianna Costa, Daniela Corongiu, Robert Goertsches, Montserrat Camina-Tato, Hans-Juergen Thiesen, Harald I Nyland, Sverre J Mørk, Xavier Montalban, Peter Rieckmann, Maria G Marrosu, Kjell-Morten Myhr, Joerg T Epplen, Janna Saarela, Saleh M Ibrahim
Affiliations

mtDNA nt13708A variant increases the risk of multiple sclerosis

Xinhua Yu et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Two mtDNA haplotypes associated with MS. (A) Evaluation of the association between four mtDNA haplotypes and MS.
The four haplotypes were constructed with nt13708 G/A and nt4216 T/C polymorphisms. The association was evaluated using the wildtype haplotype (nt13708G-nt4216T) as the control genotype, and Odds ratios and P values of the other three haplotypes were determined. (B) Phylogenetic tree of the two disease-associated mtDNA hyplotypes. The phylogenetic tree were constructed base on the mtDNA sequence of 24 sample with nt13708A-nt4216C (sample A1–A24) and 23 samples with nt13708A-nt4216T (sample B1–B23) using ClusterW softeware.
Figure 2
Figure 2. The prevalence of the nt13708 G/A polymorphism in Caucasian populations.
The data are collected form 19 Caucasian population, including 6 published (closed square), 8 in this study (closed cycle) and 5 unpublished (open cycle). The locations are indicated on the map for the European populations. For the three USA populations, the location were indicated as the text. The prevalence of the mutation are presented as the percentage of the minor allele.
See this image and copyright information in PMC

References

    1. Wallace DC. Mitochondrial defects in neurodegenerative disease. Ment Retard Dev Disabil Res Rev. 2001;7:158–166. - PubMed
    1. Kalman B, Lublin FD, Alder H. Impairment of central and peripheral myelin in mitochondrial diseases. Mult Scler. 1997;2:267–278. - PubMed
    1. Howell N, Elson JL, Chinnery PF, Turnbull DM. mtDNA mutations and common neurodegenerative disorders. Trends Genet. 2005;21:583–586. - PubMed
    1. Shoffner JM, Brown MD, Torroni A, Lott MT, Cabell MF, et al. Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients. Genomics. 1993;17:171–184. - PubMed
    1. van der Walt JM, Nicodemus KK, Martin ER, Scott WK, Nance MA, et al. Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet. 2003;72:804–811. - PMC - PubMed

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