Evidence map›Paper›PMID 34321043›Full record

SynthesisReproductive health2021

Association of endothelial nitric oxide synthase gene variants with preeclampsia.

Ghazala Shaheen, Sarwat Jahan, Nousheen Bibi, Asmat Ullah, Rani Faryal, Ali Almajwal, Tayyaba Afsar, Dara Al-Disi, Mahmoud Abulmeaty, Abdulaziz Abdullah Al Khuraif and 2 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Reproductive health, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
3.3field-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

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.

  1. Unlocking Implantation: The Role of Nitric Oxide, NOInternational journal of molecular sciences · 2025
    Pooled it
  2. Pooled it
  3. Article
  4. Association of theGenes · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Dietary supplements and vascular function in hypertensive disorders of pregnancy.Pflugers Archiv : European journal of physiology · 2023
    Review
  10. Article
  11. Article
  12. Genetic Background of Fetal Growth Restriction.International journal of molecular sciences · 2021
    Review
  13. 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

12 authors at 3 institutions in 2 countries.

Ghazala ShaheenDepartment of Animal Sciences, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Sarwat JahanDepartment of Animal Sciences, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Nousheen BibiDepartment of Bioinformatics, Shaheed Benazir Bhutto Women University, Peshawar, Pakistan.
Asmat UllahDepartment of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Rani FaryalDepartment of Microbiology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Ali AlmajwalCollege of Applied Medical Sciences, Community Health Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Tayyaba AfsarCollege of Applied Medical Sciences, Community Health Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Dara Al-DisiCollege of Applied Medical Sciences, Community Health Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Mahmoud AbulmeatyCollege of Applied Medical Sciences, Community Health Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Abdulaziz Abdullah Al KhuraifDental Biomaterials Research Chair, Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Mohammed ArshadDental Biomaterials Research Chair, Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Suhail RazakCollege of Applied Medical Sciences, Community Health Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia. smarazi@ksu.edu.sa.
King Saud University · SAQuaid-i-Azam University · PKShaheed Benazir Bhutto Women University · PK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology. The endothelial nitric oxide synthase (eNOS) gene and nitric oxide (NO) levels has been reported to be associated with PE predisposition in various populations. Therefore, present study was designed to investigate the role of NO levels and eNOS gene variants in preeclamptic women in Pakistan.

methodsA total of 600 women were evaluated, 188 of PE with mild features, 112 of PE with severe features and 300 normotensive pregnant women. NO levels were detected by Greiss reaction method and genotyping following sequencing was conducted for eNOS gene variants. Further insilico studies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation.

resultsReduced concentrations of NO were reported in all PE groups (p < 0.05) as compared to controls. The frequency of c.894 T (p.298Asp) and g.-786C alleles were significantly associated with PE. In addition, novel homozygous variant g.2051G > A was also significantly associated with PE when compared to normotensive women. Dynamic simulation studies revealed that Glu298Asp mutation destabilize the protein molecule and decrease the overall stability of eNOS protein. Molecular docking analysis of mutant promoter with transcription factors STAT3 and STAT6 proposed changes in protein regulation upon these reported mutations in upstream region of the gene.

conclusionConsidering the results of current study, the functional alterations induced by these variants may influence the bioavailability of NO and represents a genetic risk factor for increased susceptibility to PE. However, large studies or meta-analysis are necessary to validate these findings.

Indexed as

Nitric Oxide Synthase Type IIIPre-EclampsiaCase-Control StudiesFemaleGenotypeHumansMolecular Docking SimulationPakistanPregnancyNitric Oxide Synthase Type IIIEndothelial nitric oxide synthase geneNitric oxidePreeclampsiaVariants

Identifiers

PMID34321043
PMCPMC8320179
OpenAlexW3183980119

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.