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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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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)

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Title
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
Authors

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

Abstract

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.

Twitter Demographics

The data shown below were collected from the profiles of 10 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 18%
Student > Bachelor 3 18%
Student > Master 2 12%
Professor 2 12%
Lecturer 1 6%
Other 3 18%
Unknown 3 18%
Readers by discipline Count As %
Medicine and Dentistry 6 35%
Biochemistry, Genetics and Molecular Biology 5 29%
Agricultural and Biological Sciences 2 12%
Chemistry 1 6%
Unknown 3 18%

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
#2,210,128
of 12,980,529 outputs
Outputs from Clinical Epigenetics
#140
of 618 outputs
Outputs of similar age
#69,124
of 270,781 outputs
Outputs of similar age from Clinical Epigenetics
#1
of 1 outputs
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.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 270,781 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them