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A pooled study was conducted to investigate the impact of dihydrofolate reductase (DHFR) 19-bp deletion/insertion (del/ins) polymorphism on therapy containing folic acid on brain atrophy and cognitive deficit in elderly patients with mild cognitive impairment (MCI).
In geriatrics, the positive impact of folic acid-containing B vitamins on cognitive function is only evident in people with ins/ins genotype, i.e, relatively better preserved activity of dihydrofolate reductase.
A pooled study was conducted to investigate the impact of dihydrofolate reductase (DHFR) 19-bp deletion/insertion (del/ins) polymorphism on therapy containing folic acid on brain atrophy and cognitive deficit in elderly patients with mild cognitive impairment (MCI).
In this study, pooled data was utilized from 2 randomized B-vitamin trials on people with MCI (n=545) who were given either B vitamins including folic acid or a placebo for 24 months. Participants were sorted for the DHFR genotype. The Clinical Dementia Rating scale-global score (CDR-global) was the major endpoint ascertained. The memory and executive Z-scores, whole brain atrophy rate by serial magnetic resonance imaging, and Clinical Dementia Rating-sum of boxes (CDR-SOB) scores were the other endpoints ascertained.
Table 1 shows the proportion of participants with ins/ins, del/ins, and del/del genotype.
The DHFR genotypes altered the impact of B vitamins on executive function Z-scores, CDR-SOB, and CDR-global. Substantial advantages were noted in people with ins/ins genotype. Folic acid-containing supplementation elicited improvement in cognitive performance over a two-year period only in people without DHFR 19-bp deletion allele (ins/ins genotype). The interaction was not meaningful for whole brain atrophy rate and memory Z-score. Only the brain atrophy was slowed by the supplements in people with 'ins/ins' genotype who were not utilizing aspirin.
DHFR 19-bp deletion polymorphism demonstrated substantial interaction effects with folic acid-containing B-vitamin supplementation in geriatrics with MCI. Compared to people with del allele(s), people with ins/ins genotype were more likely to experience improvement in cognitive function.
Human Molecular Genetics
The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials
Yuanyuan Wu et al.
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