Evidence map›Paper›PMID 30709423›Full record

ArticleClinical epigenetics2019

TRIM4 is associated with neural tube defects based on genome-wide DNA methylation analysis.

Henan Zhang, Yi Guo, Hui Gu, Xiaowei Wei, Wei Ma, Dan Liu, Kun Yu, Wenting Luo, Ling Ma, Yusi Liu and 7 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

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  12. Neural Tube Defects andFrontiers in cell and developmental biology · 2020
    Article
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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

17 authors at 2 institutions in 1 country.

Henan ZhangKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Yi GuoKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Hui GuKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Xiaowei WeiKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Wei MaKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Dan LiuKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Kun YuKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Wenting LuoKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Ling MaKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Yusi LiuKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Jia XueKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Jieting HuangKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Yanfu WangKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Shanshan JiaKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Naixuan DongKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Hongyan WangObstetrics and Gynecology Hospital, Key Lab of Reproduction Regulation of NPFPC in SIPPR, Institute of Reproduction and Development, Fudan University, Shanghai, People's Republic of China. wanghy@fudan.edu.cn.
Zhengwei YuanKey Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China. yuanzw@hotmail.com.ORCID 0000-0003-0967-9462
China Medical University · CNFudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeural tube defects (NTDs) are complex abnormalities associated with gene-environment interactions. The underlying cause has not been determined.

methodsSpinal cord tissues from cases with NTDs and healthy controls were collected. Methylation patterns between cases and normal individuals were compared using 450K Infinium Methylation BeadChip Illumina. DNA methylation analysis by pyrosequencing (PyroMark Q96) and mRNA and protein expression were analyzed using real-time quantitative PCR and Western blotting, respectively. Next-generation and Sanger sequencing were used to determine genetic variants in the target genes.

resultsSpinal cord tissues from cases with NTDs had more hypomethylated than hypermethylated genes. Further evaluation showed that the exon 1 region of TRIM4 was hypomethylated, and TRIM4 mRNA and protein levels were significantly increased in NTDs compared to controls. A rare missense variant (rs76665876) in TRIM4 was found in 3 of the 14 NTD cases but was not related to TRIM4 expression. TRIM4 mRNA levels were significantly increased in cases with hypomethylation and without the rs76665876 variant.

conclusionThese findings suggest that spinal cord tissues in cases with NTDs had a different genome-wide methylation pattern compared to controls. Abnormal methylation patterns in TRIM4 in immunity pathways might be involved in NTD pathogenesis. Genetic variants in TRIM4 genes only slightly contribute to the etiology of human NTDs.

Indexed as

DNA MethylationUp-RegulationEpigenesis, GeneticFemaleGene Expression ProfilingGenome-Wide Association StudyGestational AgeHigh-Throughput Nucleotide SequencingHumansMaleMutation, MissenseNeural Tube DefectsTrans-ActivatorsTripartite Motif ProteinsUbiquitin-Protein LigasesWhole Genome SequencingTrans-ActivatorsTRIM4 protein, humanTripartite Motif ProteinsUbiquitin-Protein LigasesMethylationNeural tube defectsTRIM4

Identifiers

PMID30709423
PMCPMC6359777
OpenAlexW2942301764

What OpenQuestion holds

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Registered trials

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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.