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Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy

PURPOSE: Focal neurodegeneration of the optic nerve in Leber hereditary optic neuropathy (LHON) is primarily due to a maternally inherited mitochondrial DNA mutation. However, the markedly reduced penetrance of LHON and segregation pattern of visual failure within families implicates an interacting...

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Autores principales: Hudson, Gavin, Yu-Wai-Man, Patrick, Zeviani, Massimo, Chinnery, Patrick F.
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676202/
https://www.ncbi.nlm.nih.gov/pubmed/19421414
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author Hudson, Gavin
Yu-Wai-Man, Patrick
Zeviani, Massimo
Chinnery, Patrick F.
author_facet Hudson, Gavin
Yu-Wai-Man, Patrick
Zeviani, Massimo
Chinnery, Patrick F.
author_sort Hudson, Gavin
collection PubMed
description PURPOSE: Focal neurodegeneration of the optic nerve in Leber hereditary optic neuropathy (LHON) is primarily due to a maternally inherited mitochondrial DNA mutation. However, the markedly reduced penetrance of LHON and segregation pattern of visual failure within families implicates an interacting nuclear genetic locus modulating the phenotype. Folate deficiency is known to cause bilateral optic neuropathy, and defects of folate metabolism have been associated with nonarteritic ischemic optic neuropathy. METHODS: Methylenetetrahydrofolate reductase (MTHFR) catalyzes a critical step in folate metabolism, and genetic variation in MTHFR has been associated with several late-onset neurodegenerative diseases. RESULTS: We therefore determined whether functional genetic variants in MTHFR could account for the reduced penetrance in LHON by studying 414 LHON mtDNA mutation carriers. We found no evidence of association between visual failure in LHON and MTHFR polymorphisms or the MTHFR haplotype. CONCLUSIONS: Genetic variation in MTHFR does not provide an explanation for the variable phenotype in LHON.
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spelling pubmed-26762022009-05-05 Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy Hudson, Gavin Yu-Wai-Man, Patrick Zeviani, Massimo Chinnery, Patrick F. Mol Vis Research Article PURPOSE: Focal neurodegeneration of the optic nerve in Leber hereditary optic neuropathy (LHON) is primarily due to a maternally inherited mitochondrial DNA mutation. However, the markedly reduced penetrance of LHON and segregation pattern of visual failure within families implicates an interacting nuclear genetic locus modulating the phenotype. Folate deficiency is known to cause bilateral optic neuropathy, and defects of folate metabolism have been associated with nonarteritic ischemic optic neuropathy. METHODS: Methylenetetrahydrofolate reductase (MTHFR) catalyzes a critical step in folate metabolism, and genetic variation in MTHFR has been associated with several late-onset neurodegenerative diseases. RESULTS: We therefore determined whether functional genetic variants in MTHFR could account for the reduced penetrance in LHON by studying 414 LHON mtDNA mutation carriers. We found no evidence of association between visual failure in LHON and MTHFR polymorphisms or the MTHFR haplotype. CONCLUSIONS: Genetic variation in MTHFR does not provide an explanation for the variable phenotype in LHON. Molecular Vision 2009-05-01 /pmc/articles/PMC2676202/ /pubmed/19421414 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hudson, Gavin
Yu-Wai-Man, Patrick
Zeviani, Massimo
Chinnery, Patrick F.
Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy
title Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy
title_full Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy
title_fullStr Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy
title_full_unstemmed Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy
title_short Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber’s hereditary optic neuropathy
title_sort genetic variation in the methylenetetrahydrofolate reductase gene, mthfr, does not alter the risk of visual failure in leber’s hereditary optic neuropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676202/
https://www.ncbi.nlm.nih.gov/pubmed/19421414
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