Evidence map›Paper›PMID 28271401›Full record

ArticleMolecular neurobiology2018

Variants of the EAAT2 Glutamate Transporter Gene Promoter Are Associated with Cerebral Palsy in Preterm Infants.

Shavanthi Rajatileka, David Odd, Matthew T Robinson, Alexandra C Spittle, Louis Dwomoh, Maggie Williams, David Harding, Miles Wagstaff, Marie Owen, Charlene Crosby and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.5field-weighted citation impact, top 7% 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

7 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Glutamate Transport and Preterm Brain Injury.Frontiers in physiology · 2019
    Review
  6. Article
  7. Review
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

14 authors at 7 institutions in 1 country.

Shavanthi RajatilekaCentre for Research in Biosciences, Department of Applied Sciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol, BS16 1QY, UK.
David OddNeonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK.
Matthew T RobinsonCollege of Life & Environmental Sciences, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK.
Alexandra C SpittleCentre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
Louis DwomohCentre for Research in Biosciences, Department of Applied Sciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol, BS16 1QY, UK.
Maggie WilliamsBristol Genetics Laboratory, Pathology Sciences, Blood Sciences and Bristol Genetics, Southmead Hospital, Bristol, BS10 5NB, UK.
David HardingRegional Neonatal Intensive Care Unit, St Michael's Hospital, University Hospital NHS Trust, Bristol, BS2 8EG, UK.
Miles WagstaffNeonatal Intensive Care Unit, Gloucestershire Royal Hospital, Gloucestershire NHS Trust, Gloucester, GL1 3NN, UK.
Marie OwenNeonatal Intensive Care Unit, Gloucestershire Royal Hospital, Gloucestershire NHS Trust, Gloucester, GL1 3NN, UK.
Charlene CrosbyBristol Genetics Laboratory, Pathology Sciences, Blood Sciences and Bristol Genetics, Southmead Hospital, Bristol, BS10 5NB, UK.
Jared ChingNeonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK.
Elek Molnár *Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
Karen Luyt *Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK.
Anikó Váradi *Centre for Research in Biosciences, Department of Applied Sciences, Faculty of Health and Applied Sciences, University of the West of England, Bristol, BS16 1QY, UK. Aniko.Varadi@uwe.ac.uk.ORCID http://orcid.org/0000-0003-3182-5198
University of Bristol · GBUniversity of the West of England · GBGloucestershire Royal Hospital · GBSouthmead Hospital · GBNorth Bristol NHS Trust · GBSt Michael’s Hospital · GBUniversity of Exeter · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F011326/1Biotechnology and Biological Sciences Research Council BB/J015938/1
6 · The paper itself

Abstract

Preterm delivery is associated with neurodevelopmental impairment caused by environmental and genetic factors. Dysfunction of the excitatory amino acid transporter 2 (EAAT2) and the resultant impaired glutamate uptake can lead to neurological disorders. In this study, we investigated the role of single nucleotide polymorphisms (SNPs; g.-200C>A and g.-181A>C) in the EAAT2 promoter in susceptibility to brain injury and neurodisability in very preterm infants born at or before 32-week gestation. DNA isolated from newborns' dried blood spots were used for pyrosequencing to detect both SNPs. Association between EAAT2 genotypes and cerebral palsy, cystic periventricular leukomalacia and a low developmental score was then assessed. The two SNPs were concordant in 89.4% of infants resulting in three common genotypes all carrying two C and two A alleles in different combinations. However, in 10.6% of cases, non-concordance was found, generating six additional rare genotypes. The A alleles at both loci appeared to be detrimental and consequently, the risk of developing cerebral palsy increased four- and sixfold for each additional detrimental allele at -200 and -181 bp, respectively. The two SNPs altered the regulation of the EAAT2 promoter activity and glutamate homeostasis. This study highlights the significance of glutamate in the pathogenesis of preterm brain injury and subsequent development of cerebral palsy and neurodevelopmental disabilities. Furthermore, the described EAAT2 SNPs may be an early biomarker of vulnerability to neurodisability and may aid the development of targeted treatment strategies.

Indexed as

AnimalsAstrocytesCells, CulturedCerebral PalsyChild, PreschoolExcitatory Amino Acid Transporter 2FemaleGenetic VariationGlutamate Plasma Membrane Transport ProteinsHumansInfant, NewbornInfant, PrematureMalePolymorphism, Single NucleotidePromoter Regions, GeneticRatsExcitatory Amino Acid Transporter 2Glutamate Plasma Membrane Transport ProteinsSLC1A2 protein, humanBrain injuryCerebral palsyExcitatory amino acid transporter 2 (EAAT2)GlutamateGlutamate transporterNeurodevelopmental disorderPeriventricular leukomalaciaPreterm infantPromoter activityPyrosequencingSingle nucleotide polymorphism

Identifiers

PMID28271401
PMCPMC5840247
OpenAlexW2593046780

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.