Significantly, common functional polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are a risk factor for the development of late-onset AD.
The result of cumulative meta-analysis sorted by publication year was also detected a dynamic tendency of no correlation between MTHFRA1298C polymorphism and AD.
Genetic polymorphisms of brain-derived neurotrophic factor, apolipoprotein E, interleukin 1-beta, and methylenetetrahydrofolate reductase have been demonstrated to confer increased risk to both LLD and AD by studies examining either LLD or AD patients.
Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014.
The TCN2 776C → G polymorphism is negatively associated with Alzheimer's type dementia, suggesting a protective role against the disease in subjects with the 5, 10-methylenetetrahydrofolate reductase 1298AA genotype.
In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G/C (rs1800795).
To study the interplay between serum concentrations of homocysteine, steroid hormones and vitamins B and mutations in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, in association to Alzheimer's type dementia (ATD).
In AD there were significant differences of the levels of only Cys (GG, MTHFR, G1793A) and Met/Hcy (AA, MTHFD1, G1958A) whereas in PD there were more significant differences of the levels of thiols: Hcy [MTHFR: CT (C677T) and GG (G1793A); MTR, AG (A2756G)], Met [MTR, AA (A2756G)], Cys [MTR, AG (A2756G)], and Met/Hcy [MTHFR: CC, CT (C677T) and AA (A1298C), and GG (G1793A); MTHFD1 AA(G1958A); MTR AA(A2756G)].
Our data confirms the association between increased plasma Hcy concentration and AD and suggests that neither C677T nor A1298CMTHFR polymorphisms contributed to genetic susceptibility for AD in elderly individuals in the Northeast of Brazil.
Although the MTHFR gene C677T polymorphism has a significant impact on reducing enzyme activity and increasing t-Hcy concentrations, the association between the C677T polymorphism and AD remains inconclusive.