Evidence map›Paper›PMID 25565354›Full record

ArticleEpigenetics2015

DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects.

Anne Rochtus, Benedetta Izzi, Elise Vangeel, Sophie Louwette, Christine Wittevrongel, Diether Lambrechts, Yves Moreau, Raf Winand, Carla Verpoorten, Katrien Jansen and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Brain development and bioenergetic changes.Neurobiology of disease · 2024
    Review
  7. Article
  8. Article
  9. Genomic Characterization ofAnimals : an open access journal from MDPI · 2022
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Should vitamin BAnnals of the New York Academy of Sciences · 2018
    Review
  20. A unique methylation pattern co-segregates with neural tube defect statuses in Han Chinese pedigrees.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 3 countries.

Anne Rochtusa Department of Cardiovascular Sciences; Center for Molecular and Vascular Biology ; University of Leuven ; Leuven , Belgium.
Benedetta Izzi
Elise Vangeel
Sophie Louwette
Christine Wittevrongel
Diether Lambrechts
Yves Moreau
Raf Winand
Carla Verpoorten
Katrien Jansen
Chris Van Geet
Kathleen Freson
KU Leuven · BECenter for Vascular Biology Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different HOX genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX clusters, 26 CpGs were differentially methylated (P-value < 0.05; β-difference > 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the HOXA and HOXB clusters, with the most profound difference for 3 CpGs within the HOXB7 gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9-16.9%; P-value < 0.0001) independent of the MTHFR 667C>T genotype. Significant HOXB7 hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways.

Indexed as

DNA MethylationAdultAnimalsCpG IslandsEpigenesis, GeneticFemaleGene Expression Regulation, DevelopmentalGenomeHomeodomain ProteinsHumansInfant, NewbornMaleMeningomyeloceleMethylenetetrahydrofolate Reductase (NADPH2)Polymorphism, Single NucleotideZebrafishHomeodomain ProteinsHOXB7 protein, humanMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanDNA methylationepigeneticsHOXB7HOX genesMyelomeningoceleneural tube defects

Identifiers

PMID25565354
PMCPMC4622610
OpenAlexW1873259742

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.