Association of Fetal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects: A Systematic Review and Update Meta-Analysis

Tabatabaei, Razieh Sadat; Fatahi-Meibodi, Neda; Meibodi, Bahare; Javaheri, Atiyeh; Abbasi, Hajar; Hadadan, Amaneh; Bahrami, Reza; Mirjalili, Seyed Reza; Karimi-Zarchi, Mojgan; Neámatzadeh, Hossein

doi:10.1080/15513815.2020.1775734

Cited by 17 publications

(9 citation statements)

References 43 publications

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“…The results of the present study indicated that there was no association between maternal and fetal MTHFR C677T polymorphism with the risk of NTDs in the East Asian population. Our results opposed those obtained in the previous studies which have verified the association of MTHFR polymorphism and the risk of NTDs in the Asian population (28,30). This contradiction might be due to the omission of non-English language studies in this meta-analysis study which included only original articles and excluded letters, short communication articles, and reports.…”

Section: Discussioncontrasting

confidence: 99%

Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

2021

ircmj

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Background: Neural tube defects (NTDs) are classed as multifactorial birth defects of the brain and spinal cord that arise during embryonic development. Although the etiology is not well understood, NTDs are reported to be prevented by maternal folic acid supplementation before and during early pregnancy. This meta-analysis study aimed to assess the association between fetal and maternal methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with the risk of NTDs. Methods: The PubMed, Scopus, and Springer Link databases were searched (from March 2000 to November 2020) for the literature on the association between MTHFR C677T and MTRR A66G polymorphisms with the risk of NTDs. Results: In total, 33 studies were reviewed in the present study, and it was revealed that, unlike MTRR A66G polymorphism, MTHFR C677T was statistically associated with the risk of NTDs in the overall population. The results of subgroup analysis showed that the Indian subcontinent subgroup with maternal MTHFR C677T polymorphism and the European subgroup with fetal MTHFR C677T polymorphism was significantly susceptible to NTDs. Conclusion: The obtained results revealed that, unlike MTRR A66G, maternal and fetal MTHFR C677T polymorphism was significantly associated with NTDs. Subgroup analysis also demonstrated that folic acid deprivation can be considered the main cause of MTHFR C677T polymorphism in some areas.

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Section: Discussioncontrasting

confidence: 99%

Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

2021

ircmj

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“…67,68 Mild to moderate hyperhomocysteinemia has been previously implicated as a risk factor for hypertension 69 and cardiovascular disease. 70 Presence of these variants, with and without mildly elevated levels of homocysteine, has been studied in relation to several multifactorial disorders including recurrent pregnancy loss, 71 neural tube defects and congenital anomalies, 72 cancer, 73 glaucoma, and neurodevelopmental disorders, notably autism. 74 However, because the 677 C > T variant has been linked to AD or vascular dementia in multiple GWAS, we hypothesized that it is playing a role specifically in the brain.…”

Section: Discussionmentioning

confidence: 99%

The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice

Reagan

Christensen

Graham

et al. 2022

J Cereb Blood Flow Metab

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Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimer’s disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in MTHFR, notably 677 C > T, are associated with dementias, but no mouse model existed to identify mechanisms by which MTHFR677C > T increases risk. Therefore, MODEL-AD created a novel knock-in (KI) strain carrying the Mthfr677C > T allele on the C57BL/6J background ( Mthfr677C > T) to characterize morphology and function perturbed by the variant. Consistent with human clinical data, Mthfr677C > T mice have reduced enzyme activity in the liver and elevated plasma homocysteine levels. MTHFR enzyme activity is also reduced in the Mthfr677C > T brain. Mice showed reduced tissue perfusion in numerous brain regions by PET/CT as well as significantly reduced vascular density, pericyte number and increased GFAP-expressing astrocytes in frontal cortex. Electron microscopy revealed cerebrovascular damage including endothelial and pericyte apoptosis, reduced luminal size, and increased astrocyte and microglial presence in the microenvironment. Collectively, these data support a mechanism by which variations in MTHFR perturb cerebrovascular health laying the foundation to incorporate our new Mthfr677C > T mouse model in studies examining genetic susceptibility for cerebrovascular dysfunction in ADRDs.

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“…Folate and other B vitamins play important roles in the one-carbon metabolism pathway, which is associated with DNA methylation, synthesis and impaired DNA repair (Pan et al, 2019). The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is involved in the circulation form of folate as it catalyzes the irreversible reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (Maruti et al, 2009;Soleimani-Jadidi et al, 2020;Tabatabaei et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Associations of MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) Polymorphisms with Susceptibility to Bladder Cancer: A Systematic Review and Meta-Analysis

Farshid

Alijanpour

Barahman

et al. 2022

Asian Pac J Cancer Prev

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Association of Fetal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects: A Systematic Review and Update Meta-Analysis

Cited by 17 publications

References 43 publications

Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice

Associations of MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) Polymorphisms with Susceptibility to Bladder Cancer: A Systematic Review and Meta-Analysis

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