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Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment()
A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757723/ https://www.ncbi.nlm.nih.gov/pubmed/24179750 http://dx.doi.org/10.1016/j.nicl.2012.09.012 |
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author | Rajagopalan, Priya Jahanshad, Neda Stein, Jason L. Hua, Xue Madsen, Sarah K. Kohannim, Omid Hibar, Derrek P. Toga, Arthur W. Jack, Clifford R. Saykin, Andrew J. Green, Robert C. Weiner, Michael W. Bis, Joshua C. Kuller, Lewis H. Riverol, Mario Becker, James T. Lopez, Oscar L. Thompson, Paul M. |
author_facet | Rajagopalan, Priya Jahanshad, Neda Stein, Jason L. Hua, Xue Madsen, Sarah K. Kohannim, Omid Hibar, Derrek P. Toga, Arthur W. Jack, Clifford R. Saykin, Andrew J. Green, Robert C. Weiner, Michael W. Bis, Joshua C. Kuller, Lewis H. Riverol, Mario Becker, James T. Lopez, Oscar L. Thompson, Paul M. |
author_sort | Rajagopalan, Priya |
collection | PubMed |
description | A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75 ± 7.1 years) scanned with brain MRI and genotyped as part of Alzheimer's Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76 ± 5.5 years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR ‘T’ alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2–8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5–1.5% per T allele at 1 year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5–12% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI. |
format | Online Article Text |
id | pubmed-3757723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-37577232013-10-31 Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() Rajagopalan, Priya Jahanshad, Neda Stein, Jason L. Hua, Xue Madsen, Sarah K. Kohannim, Omid Hibar, Derrek P. Toga, Arthur W. Jack, Clifford R. Saykin, Andrew J. Green, Robert C. Weiner, Michael W. Bis, Joshua C. Kuller, Lewis H. Riverol, Mario Becker, James T. Lopez, Oscar L. Thompson, Paul M. Neuroimage Clin Article A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75 ± 7.1 years) scanned with brain MRI and genotyped as part of Alzheimer's Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76 ± 5.5 years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR ‘T’ alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2–8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5–1.5% per T allele at 1 year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5–12% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI. Elsevier 2012-10-04 /pmc/articles/PMC3757723/ /pubmed/24179750 http://dx.doi.org/10.1016/j.nicl.2012.09.012 Text en © 2012 The Authors 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 author and source are credited. |
spellingShingle | Article Rajagopalan, Priya Jahanshad, Neda Stein, Jason L. Hua, Xue Madsen, Sarah K. Kohannim, Omid Hibar, Derrek P. Toga, Arthur W. Jack, Clifford R. Saykin, Andrew J. Green, Robert C. Weiner, Michael W. Bis, Joshua C. Kuller, Lewis H. Riverol, Mario Becker, James T. Lopez, Oscar L. Thompson, Paul M. Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
title | Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
title_full | Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
title_fullStr | Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
title_full_unstemmed | Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
title_short | Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
title_sort | common folate gene variant, mthfr c677t, is associated with brain structure in two independent cohorts of people with mild cognitive impairment() |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757723/ https://www.ncbi.nlm.nih.gov/pubmed/24179750 http://dx.doi.org/10.1016/j.nicl.2012.09.012 |
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