Observational studyThe American journal of clinical nutrition2015
Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults.
Observational study in The American journal of clinical nutrition, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01231958 (The Boston Puerto Rican Health Study), which is not on this map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Boston Puerto Rican Health Study: Center for Population Health and Health Disparities
Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- 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.Human molecular genetics · 2022Trial
- Trial
- B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial.The journal of prevention of Alzheimer's disease · 2017Trial
- Folic acid supplementation on congenital heart disease and its dual character.Current research in pharmacology and drug discovery · 2025Review
- Article
- Article
- Overview of Neural Tube Defects: Gene-Environment Interactions, Preventative Approaches and Future Perspectives.Biomedicines · 2022Review
- Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets RevealsFrontiers in aging neuroscience · 2022Article
- Association Between Folate Metabolites and the Development of Food Allergy in Children.The journal of allergy and clinical immunology. In practice · 2020Article
- The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1.Frontiers in genetics · 2019Review
- Oral findings and its association with prenatal and perinatal factors in newborns.Korean journal of pediatrics · 2018Article
- The Evolving Role of Multivitamin/Multimineral Supplement Use among Adults in the Age of Personalized Nutrition.Nutrients · 2018Review
- Vitamins Associated with Brain Aging, Mild Cognitive Impairment, and Alzheimer Disease: Biomarkers, Epidemiological and Experimental Evidence, Plausible Mechanisms, and Knowledge Gaps.Advances in nutrition (Bethesda, Md.) · 2017Review
- The adverse effects of an excessive folic acid intake.European journal of clinical nutrition · 2017Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundFolate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously.
objectiveWe examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate.
designThis was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests.
resultsThe prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: β ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (β ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (β = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (β-interaction = 0.26 ± 0.13, P < 0.05).
conclusionsThis study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.
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