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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2012
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.
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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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