Evidence map›Paper›PMID 39439802›Full record

SynthesisFrontiers in immunology2024

Using genetics to explore complement C5 as a druggable protein in periodontitis.

Zoheir Alayash, Sebastian-Edgar Baumeister, Birte Holtfreter, Thomas Kocher, Hansjörg Baurecht, Benjamin Ehmke, Stefan Lars Reckelkamm, Michael Nolde

Abstract readMeta-Analysis
In one paragraph

Synthesis in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Proteome-Guided Drug Target Discovery for Periodontitis.Journal of clinical periodontology · 2026
    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

8 authors.

Zoheir AlayashInstitute of Health Services Research in Dentistry, University of Münster, Münster, Germany.
Sebastian-Edgar BaumeisterInstitute of Health Services Research in Dentistry, University of Münster, Münster, Germany.
Birte HoltfreterDepartment of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
Thomas KocherDepartment of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
Hansjörg BaurechtDepartment of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
Benjamin EhmkeClinic for Periodontology and Conservative Dentistry, University of Münster, Münster, Germany.
Stefan Lars ReckelkammInstitute of Health Services Research in Dentistry, University of Münster, Münster, Germany.
Michael NoldeInstitute of Health Services Research in Dentistry, University of Münster, Münster, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aim: An excessively activated or dysregulated complement system has been proven to be a vital contributor to the pathogenesis of periodontitis. It has been previously hypothesized that inhibiting the activity of complement component C5 by targeting the C5a receptor is a powerful candidate for treating periodontitis. Here, we apply the drug target instrumental variable (IV) approach to investigate the therapeutic effect of genetically proxied inhibition of C5 on periodontitis. Method: In our primary analysis, we used 26 independent 'cis' single nucleotide polymorphisms as IVs from the vicinity of the encoding locus of C5 that are associated with plasma C5 levels. In a secondary analysis, we assess the validity of our primary findings, exploring the involvement of alternative downstream biomarkers, interleukin 17 (IL-17), interleukin 1β (IL-1β), and tumor necrosis factor (TNF). Summary statistics of plasma levels (C5, IL-17, IL-1β, and TNF) were obtained from a genome-wide association study (GWAS) of 35,559 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis. Results: In our primary approach, inhibiting C5 reduced the risk of periodontitis (Odds ratio 0.89 per 1 standard deviation reduction in C5; 95% confidence Interval 0.80-0.98, Conclusions: The findings from our study suggest that C5 inhibition may reduce the risk of periodontitis, prioritizing C5 inhibitors as a potential adjunctive therapeutic intervention in this disease.

Indexed as

Complement C5Genome-Wide Association StudyPeriodontitisBiomarkersGenetic Predisposition to DiseaseHumansInterleukin-17Interleukin-1betaPolymorphism, Single NucleotideBiomarkersComplement C5Interleukin-17Interleukin-1betacomplement C5drug discoveryimmunomodulationinstrumental variable analysisperiodontitis

Identifiers

PMID39439802
PMCPMC11493656

What Socratic holds

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LicenceCC BY
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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 Socratic graph.