High homocysteine and epistasis between MTHFR and APOE: association with cognitive performance in the elderly

Polito, Letizia; Poloni, Tino Emanuele; Vaccaro, Roberta; Abbondanza, Simona; Mangieri, Michela; Davin, Annalisa; Villani, Simona; Guaita, Antonio

doi:10.1016/j.exger.2016.01.005

Cited by 20 publications

(15 citation statements)

References 47 publications

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“…Differences in age and average homocysteine concentration might account for some of the differences between our findings and those of Chin et al [ 35 ]. Some evidence suggests that higher homocysteine levels may be more closely associated with certain cognitive domains, such as executive functioning and processing speed than with other cognitive domains [ 36 , 37 ]. The limited cognitive testing available in the NHANES dataset we used might have precluded our finding an association between homocysteine concentration and cognitive function, in that we assessed cognitive function with only the DSC [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori moderates the association between 5-MTHF concentration and cognitive function in older adults

et al. 2018

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ObjectiveTo explore potential interactions between folate-cycle factors and Helicobacter pylori seropositivity in the prediction of cognitive function.MethodsWe used data obtained from the 1999–2000 continuous National Health and Nutrition Examination Survey produced by the United States’ Centers for Disease Control and Prevention. Using Ordinary Least Squares regression, we tested for associations between multiple folate-cycle factors, Helicobacter pylori seropositivity, and cognitive function assessed by the digit symbol coding subtest of the Wechsler Adult Intelligence Scale-III. We then tested for interactions between each of the folate-cycle factors and Helicobacter pylori in the prediction of cognitive function.ResultsAlthough Helicobacter pylori seropositivity, 5-methyltetrahydrofolate, vitamin B-12, and homocysteine were not associated with performance on the digit symbol coding task, Helicobacter pylori seropositivity interacted with 5-methyltetrahydrofolate concentration to predict performance on the digit symbol coding task. The Helicobacter pylori seropositive group performed worse on the digit symbol coding task as 5-methyltetrahydrofolate concentration decreased.ConclusionThe interaction between Helicobacter pylori seropositivity and reduced folate-cycle factor 5-methyltetrahydrofolate might impair aspects of cognitive function.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori moderates the association between 5-MTHF concentration and cognitive function in older adults

et al. 2018

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“…Homocysteine in high concentration may deteriorate dementia and serve as a critical regulation function in DNA methylation modification though modulating the activity of methyltransferase [ 43 , 44 ]. Our result is in line with the previous evidence [ 45 , 46 ], although no correlation between homocysteine and OPRD1 methylation is identified.…”

Section: Discussionmentioning

confidence: 99%

Elevated OPRD1 promoter methylation in Alzheimer’s disease patients

Wang

Liu

et al. 2017

PLoS ONE

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Aberrant DNA methylation has been observed in the patients with Alzheimer’s disease (AD), a common neurodegenerative disorder in the elderly. OPRD1 encodes the delta opioid receptor, a member of the opioid family of G-protein-coupled receptors. In the current study, we compare the DNA methylation levels of OPRD1 promoter CpG sites (CpG1, CpG2, and CpG3) between 51 AD cases and 63 controls using the bisulfite pyrosequencing technology. Our results show that significantly higher CpG3 methylation is found in AD cases than controls. Significant associations are found between several biochemical parameters (including HDL-C and ALP) and CpG3 methylation. Subsequent luciferase reporter gene assay shows that DNA fragment containing the three OPRD1 promoter CpGs is able to regulate gene expression. In summary, our results suggest that OPRD1 promoter hypermethylation is associated with the risk of AD.

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“…In addition, we analyzed the possible confounding roles of serum biomarkers in each MTHFR functional group. Several studies have shown that the effect of the MTHFR genotype in predicting AD cognitive test outcomes can be confounded by factors including serum homocysteine level, ApoE genotype status (Polito et al, ), serum ApoE level (Roussotte et al, ), disease stage, in vivo amyloid burden, and endothelial integrity (Ma et al, ).…”

Section: Discussionmentioning

confidence: 99%

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white‐matter integrity in Alzheimer's disease

Chang

Hsu

Tsai

et al. 2017

Human Brain Mapping

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The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

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High homocysteine and epistasis between MTHFR and APOE: association with cognitive performance in the elderly

Cited by 20 publications

References 47 publications

Helicobacter pylori moderates the association between 5-MTHF concentration and cognitive function in older adults

Helicobacter pylori moderates the association between 5-MTHF concentration and cognitive function in older adults

Elevated OPRD1 promoter methylation in Alzheimer’s disease patients

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white‐matter integrity in Alzheimer's disease

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