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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.
Friday,2013-11-08 12:01 America/Los_Angeles — poolea2
| Title | Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Rajagopalan, P, Jahanshad, N, Stein, JL, Hua, X, Madsen, SK, Kohannim, O, Hibar, DP, Toga, AW, Jack, CR, Saykin, AJ, Green, RC, Weiner, MW, Bis, JC, Kuller, LH, Riverol, M, Becker, JT, Lopez, OL, Thompson, PM |
| Corporate/Institutional Authors | Alzheimer's Disease Neuroimaging Initiative (ADNI), Cardiovascular Health Study (CHS) |
| Journal | Neuroimage Clin |
| Volume | 1 |
| Issue | 1 |
| Pagination | 179-87 |
| Date Published | 2012 |
| ISSN | 2213-1582 |
| Abstract | <p>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. </p> |
| DOI | 10.1016/j.nicl.2012.09.012 |
| Alternate Journal | Neuroimage Clin |
| PubMed ID | 24179750 |
| PubMed Central ID | PMC3757723 |
| Grant List | K01 AG030514 / AG / NIA NIH HHS / United States T15 LM007356 / LM / NLM NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States T32 GM008042 / GM / NIGMS NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States R01 EB008281 / EB / NIBIB NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States |