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Inducing Apical Periodontitis in Mice
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Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis.

T H Harris1,2, M R Wallace3,4, H Huang1

  • 1Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA.

JDR Clinical and Translational Research
|July 19, 2019
PubMed
Summary
This summary is machine-generated.

This study links P2RX7 gene variants to localized aggressive periodontitis (LAP) and altered immune responses. Inhibiting the P2X7 receptor increased P2RX7 mRNA, suggesting a feedback loop in LAP.

Keywords:
cytokine(s)geneticsinflammationmolecular geneticsperiodontal diseasessingle nucleotide polymorphism

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Area of Science:

  • Immunology
  • Genetics
  • Periodontology

Background:

  • Localized aggressive periodontitis (LAP) is a severe inflammatory gum disease.
  • The P2X7 receptor (P2X7R) is implicated in inflammatory processes.
  • Understanding genetic factors influencing P2X7R function in LAP is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of P2X7 receptor (P2X7R) functional diplotypes in localized aggressive periodontitis (LAP).
  • To analyze the association between P2RX7 gene polymorphisms and immune responses in LAP patients.
  • To explore the effect of P2X7R activation and inhibition on inflammatory markers and gene expression.

Main Methods:

  • Genotyping of three P2RX7 single-nucleotide polymorphisms (SNPs) in 95 LAP patients and 76 healthy controls.
  • Stimulation of peripheral blood samples with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to assess P2X7R activity.
  • Measurement of inflammatory markers (cytokines/chemokines) using Luminex assay and P2RX7 mRNA levels via real-time quantitative PCR.

Main Results:

  • Significant associations were found between P2RX7 diplotypes and LPS-stimulated blood cytokine/chemokine levels in LAP patients compared to controls.
  • P2X7R activation by ATP significantly altered IL-1β and IL-12p40 concentrations in both groups.
  • Inhibition of P2X7R led to a significant increase in P2RX7 mRNA levels in both LAP and healthy individuals, indicating a feedback mechanism.

Conclusions:

  • P2RX7 functional diplotypes are associated with localized aggressive periodontitis (LAP) and altered in vitro immune responses.
  • P2X7 receptor activation influences key inflammatory mediators in LAP.
  • A feedback loop exists where P2X7R inhibition upregulates P2RX7 mRNA expression, offering potential therapeutic targets.