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Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration

BACKGROUND: Mitochondrial dysfunction, oxidative damage and the accumulation of somatic mutations in mitochondrial DNA (mtDNA) have been associated with certain neurodegenerative disorders. Previous studies have also provided controversial results on the association of mtDNA haplogroups with suscept...

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Autores principales: Krüger, Johanna, Hinttala, Reetta, Majamaa, Kari, Remes, Anne M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830999/
https://www.ncbi.nlm.nih.gov/pubmed/20181062
http://dx.doi.org/10.1186/1750-1326-5-8
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author Krüger, Johanna
Hinttala, Reetta
Majamaa, Kari
Remes, Anne M
author_facet Krüger, Johanna
Hinttala, Reetta
Majamaa, Kari
Remes, Anne M
author_sort Krüger, Johanna
collection PubMed
description BACKGROUND: Mitochondrial dysfunction, oxidative damage and the accumulation of somatic mutations in mitochondrial DNA (mtDNA) have been associated with certain neurodegenerative disorders. Previous studies have also provided controversial results on the association of mtDNA haplogroups with susceptibility to Alzheimer's disease (AD), but possible relationships between mtDNA and frontotemporal lobar degeneration (FTLD) have been less frequently studied. METHODS: We analysed the role of mtDNA and its maintenance enzymes in 128 early-onset AD (eoAD) and in 66 FTLD cases. Patients and 99 controls were collected from a defined region of Finland, that of Northern Ostrobothnia, for the determination of mtDNA haplogroups and the analysis of two common mtDNA mutations (m.3243A>G, m.8344A>G). In addition, screening was performed for five common POLG1 mutations (T251I, A467T, P587L, W748S and Y955C) and all the coding exons of the PEO1 and ANT1 genes were screened for mutations. RESULTS: The frequency of haplogroup cluster IWX was 2.3 fold higher among the FTLD cases than in the controls (OR 2.69, 95% CI 1.09-6.65, p = 0.028). The frequency of mtDNA haplogroups or clusters did not differ between the eoAD cases and controls. The two mtDNA mutations and five POLG1 mutations were absent in the eoAD and FTLD patients. No pathogenic mutations were found in the PEO1 or ANT1 genes. CONCLUSIONS: We conclude that the haplogroup cluster IWX was associated with FTLD in our cohort. Further studies in other ethnically distinct cohorts are needed to clarify the contribution of mtDNA haplogroups to FTLD and AD.
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spelling pubmed-28309992010-03-03 Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration Krüger, Johanna Hinttala, Reetta Majamaa, Kari Remes, Anne M Mol Neurodegener Research Article BACKGROUND: Mitochondrial dysfunction, oxidative damage and the accumulation of somatic mutations in mitochondrial DNA (mtDNA) have been associated with certain neurodegenerative disorders. Previous studies have also provided controversial results on the association of mtDNA haplogroups with susceptibility to Alzheimer's disease (AD), but possible relationships between mtDNA and frontotemporal lobar degeneration (FTLD) have been less frequently studied. METHODS: We analysed the role of mtDNA and its maintenance enzymes in 128 early-onset AD (eoAD) and in 66 FTLD cases. Patients and 99 controls were collected from a defined region of Finland, that of Northern Ostrobothnia, for the determination of mtDNA haplogroups and the analysis of two common mtDNA mutations (m.3243A>G, m.8344A>G). In addition, screening was performed for five common POLG1 mutations (T251I, A467T, P587L, W748S and Y955C) and all the coding exons of the PEO1 and ANT1 genes were screened for mutations. RESULTS: The frequency of haplogroup cluster IWX was 2.3 fold higher among the FTLD cases than in the controls (OR 2.69, 95% CI 1.09-6.65, p = 0.028). The frequency of mtDNA haplogroups or clusters did not differ between the eoAD cases and controls. The two mtDNA mutations and five POLG1 mutations were absent in the eoAD and FTLD patients. No pathogenic mutations were found in the PEO1 or ANT1 genes. CONCLUSIONS: We conclude that the haplogroup cluster IWX was associated with FTLD in our cohort. Further studies in other ethnically distinct cohorts are needed to clarify the contribution of mtDNA haplogroups to FTLD and AD. BioMed Central 2010-02-02 /pmc/articles/PMC2830999/ /pubmed/20181062 http://dx.doi.org/10.1186/1750-1326-5-8 Text en Copyright ©2010 Krüger et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Krüger, Johanna
Hinttala, Reetta
Majamaa, Kari
Remes, Anne M
Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration
title Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration
title_full Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration
title_fullStr Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration
title_full_unstemmed Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration
title_short Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration
title_sort mitochondrial dna haplogroups in early-onset alzheimer's disease and frontotemporal lobar degeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830999/
https://www.ncbi.nlm.nih.gov/pubmed/20181062
http://dx.doi.org/10.1186/1750-1326-5-8
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