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No evidence for association of MTHFR 677C>T and 1298A>C variants with placental DNA methylation

Overview of attention for article published in Clinical Epigenetics, March 2018
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No evidence for association of MTHFR 677C>T and 1298A>C variants with placental DNA methylation
Published in
Clinical Epigenetics, March 2018
DOI 10.1186/s13148-018-0468-1
Pubmed ID

Giulia F. Del Gobbo, E. Magda Price, Courtney W. Hanna, Wendy P. Robinson


5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon metabolism that ensures the availability of methyl groups for methylation reactions. Two single-nucleotide polymorphisms (SNPs) in the MTHFR gene, 677C>T and 1298A>C, result in a thermolabile enzyme with reduced function. These variants, in both the maternal and/or fetal genes, have been associated with pregnancy complications including miscarriage, neural tube defects (NTDs), and preeclampsia (PE), perhaps due to altered capacity for DNA methylation (DNAm). In this study, we assessed the association between MTHFR 677TT and 1298CC genotypes and risk of NTDs, PE, or normotensive intrauterine growth restriction (nIUGR). Additionally, we assessed whether these high-risk genotypes are associated with altered DNAm in the placenta. In 303 placentas screened for this study, we observed no significant association between the occurrence of NTDs (N = 55), PE (early-onset: N = 28, late-onset: N = 20), or nIUGR (N = 21) and placental (fetal) MTHFR 677TT or 1298CC genotypes compared to healthy pregnancies (N = 179), though a trend of increased 677TT genotype in PE/IUGR together was observed (OR 2.53, p = 0.048). DNAm was profiled in 10 high-risk 677 (677TT + 1298AA), 10 high-risk 1298 (677CC + 1298CC), and 10 reference (677CC + 1298AA) genotype placentas. Linear modeling identified no significantly differentially methylated sites between high-risk 677 or 1298 and reference placentas at a false discovery rate < 0.05 and Δβ ≥ 0.05 using the Illumina Infinium HumanMethylation450 BeadChip. Using a differentially methylated region analysis or separating cytosine-guanine dinucleotides (CpGs) by CpG density to reduce multiple comparisons also did not identify differential methylation. Additionally, there was no consistent evidence for altered methylation of repetitive DNA between high-risk and reference placentas. We conclude that large-scale, genome-wide disruption in DNAm does not occur in placentas with the high-risk MTHFR 677TT or 1298CC genotypes. Furthermore, there was no evidence for an association of the 1298CC genotype and only a tendency to higher 677TT in pregnancy complications of PE/IUGR. This may be due to small sample sizes or folate repletion in our Canadian population attenuating effects of the high-risk MTHFR variants. However, given our results and the conflicting results in the literature, investigations into alternative mechanisms that may explain the link between MTHFR variants and pregnancy complications, or in populations at risk of folate deficiencies, are warranted.

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Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 23%
Student > Ph. D. Student 5 19%
Student > Master 3 12%
Other 2 8%
Professor 2 8%
Other 4 15%
Unknown 4 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 31%
Medicine and Dentistry 7 27%
Agricultural and Biological Sciences 2 8%
Unspecified 1 4%
Computer Science 1 4%
Other 3 12%
Unknown 4 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 May 2018.
All research outputs
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Outputs from Clinical Epigenetics
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Outputs of similar age
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Outputs of similar age from Clinical Epigenetics
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Altmetric has tracked 12,980,529 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 618 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one has done well, scoring higher than 77% of its peers.
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