mtDNA nt13708A Variant Increases the Risk of Multiple Sclerosis

被引：72

作者：

Yu, Xinhua ^{[1
]}

Koczan, Dirk ^{[2
]}

Sulonen, Anna-Maija ^{[3
]}

Akkad, Denis A. ^{[4
]}

Kroner, Antje ^{[5
]}

Comabella, Manuel ^{[6
]}

Costa, Gianna ^{[7
]}

Corongiu, Daniela ^{[7
]}

Goertsches, Robert ^{[2
]}

Camina-Tato, Montserrat ^{[6
]}

Thiesen, Hans-Juergen ^{[2
]}

Nyland, Harald I. ^{[8
,9
]}

Mork, Sverre J. ^{[10
]}

Montalban, Xavier ^{[6
]}

Rieckmann, Peter ^{[5
]}

Marrosu, Maria G. ^{[7
]}

Myhr, Kjell-Morten ^{[8
,9
]}

Epplen, Joerg T. ^{[4
]}

Saarela, Janna ^{[3
]}

Ibrahim, Saleh M. ^{[1
]}

机构：

[1] Univ Rostock, Sect Immunogenet, Rostock, Germany

[2] Univ Rostock, Dept Immunol, Rostock, Germany

[3] Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland

[4] Ruhr Univ, IGSN, Dept Human Genet, Bochum, Germany

[5] Univ Wurzburg, Dept Neurol, Clin Res Grp MS & Neuroimmunol, Wurzburg, Germany

[6] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Unit Neuroimmunol Clin, Barcelona, Spain

[7] Univ Cagliari, Dipart Sci Cardiovascol Neurol, Centro Sclerosi Multipla, Cagliari, Italy

[8] Univ Bergen, Haukeland Univ Hosp, Dept Neurol, Bergen, Norway

[9] Univ Bergen, Dept Clin Med, Bergen, Norway

[10] Univ Bergen, Gades Inst, Haukeland Univ Hosp, Dept Pathol, Bergen, Norway

来源：

PLOS ONE | 2008年 / 3卷 / 02期

关键词：

D O I：

10.1371/journal.pone.0001530

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 nt 13708A allele was associated with an increased risk of MS (OR = 1.71, 95% Cl 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.

引用

页数：7

共 33 条

[1] Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production [J].