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Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis.
JDR Clin Trans Res 2019; :2380084419863789JC

Abstract

AIM

The purpose of this study was to test for the role of the P2X7 receptor in localized aggressive periodontitis (LAP).

METHODS

Peripheral blood was obtained from 95 subjects with LAP and 76 healthy unrelated controls (HUCs). Three P2RX7 single-nucleotide polymorphisms (rs1718119, rs2230911, and rs3751143) were genotyped from these subjects, and their peripheral blood samples were stimulated with lipopolysaccharide (LPS) from Escherichia coli and tested for inflammatory markers. The 3 P2RX7 single-nucleotide polymorphisms were in found to be in perfect linkage disequilibrium, and a total of 4 haplotypes and 9 diplotypes were identified among all subjects. For both subject populations, the 9 diplotypes were grouped into 4 functional groups and tested for association with subject inflammatory response. To specifically study the effects of extrinsic activation of the P2X7 receptor in LAP, peripheral blood samples from were stimulated under 3 treatments: LPS, LPS + ATP, and LPS +ATP+ P2X7 selective inhibitor. The effects of these treatments on P2X7 receptor activity were measured through Luminex protein assay. Last, to test whether receptor stimulation was related to P2RX7 expression, relative mRNA levels of P2RX7 were quantified with real-time quantitative polymerase chain reaction.

RESULTS

Several associations between the P2RX7 diplotypes and LPS-stimulated blood chemokine/cytokine levels were found between the LAP and HUC populations (P < 0.05). P2X7 activation resulted in statistically significant differences in IL-1β and IL-12p40 concentrations for both subject populations. The relative P2RX7 mRNA levels increased significantly after addition of its inhibitor for both LAP and HUC populations.

CONCLUSIONS

This study detected an association between P2RX7 functional diplotypes and in vitro immune response of whole blood from subjects with LAP. In addition, we found that inhibition of the activated P2X7 receptor leads to increased P2RX7 mRNA levels, suggesting a feedback loop (ClinicalTrials.gov NCT01330719).

KNOWLEDGE TRANSFER STATEMENT

The results of this study suggest that P2RX7 functional diplotypes are associated with LAP and their in vitro immune response to bacteria. Ongoing studies to uncover the mechanistic link between P2RX7 and LAP phenotypes could lead to the development of preventive approaches for susceptible subjects.

Authors+Show Affiliations

1 Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA. 2 Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.3 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA. 4 University of Florida Genetics Institute, Gainesville, FL, USA.1 Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA.3 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.1 Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA. 5 Current affiliation: Division of Periodontology, Department of Oral Health Practice, College of Dentistry, University of Kentucky, Lexington, KY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31319038

Citation

Harris, T H., et al. "Associations of P2RX7 Functional Diplotypes With Localized Aggressive Periodontitis." JDR Clinical and Translational Research, 2019, p. 2380084419863789.
Harris TH, Wallace MR, Huang H, et al. Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis. JDR Clin Trans Res. 2019.
Harris, T. H., Wallace, M. R., Huang, H., Li, H., & Shaddox, L. M. (2019). Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis. JDR Clinical and Translational Research, p. 2380084419863789. doi:10.1177/2380084419863789.
Harris TH, et al. Associations of P2RX7 Functional Diplotypes With Localized Aggressive Periodontitis. JDR Clin Trans Res. 2019 Jul 18;2380084419863789. PubMed PMID: 31319038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis. AU - Harris,T H, AU - Wallace,M R, AU - Huang,H, AU - Li,H, AU - Shaddox,L M, Y1 - 2019/07/18/ PY - 2019/7/19/entrez PY - 2019/7/19/pubmed PY - 2019/7/19/medline KW - cytokine(s) KW - genetics KW - inflammation KW - molecular genetics KW - periodontal diseases KW - single nucleotide polymorphism SP - 2380084419863789 EP - 2380084419863789 JF - JDR clinical and translational research JO - JDR Clin Trans Res N2 - AIM: The purpose of this study was to test for the role of the P2X7 receptor in localized aggressive periodontitis (LAP). METHODS: Peripheral blood was obtained from 95 subjects with LAP and 76 healthy unrelated controls (HUCs). Three P2RX7 single-nucleotide polymorphisms (rs1718119, rs2230911, and rs3751143) were genotyped from these subjects, and their peripheral blood samples were stimulated with lipopolysaccharide (LPS) from Escherichia coli and tested for inflammatory markers. The 3 P2RX7 single-nucleotide polymorphisms were in found to be in perfect linkage disequilibrium, and a total of 4 haplotypes and 9 diplotypes were identified among all subjects. For both subject populations, the 9 diplotypes were grouped into 4 functional groups and tested for association with subject inflammatory response. To specifically study the effects of extrinsic activation of the P2X7 receptor in LAP, peripheral blood samples from were stimulated under 3 treatments: LPS, LPS + ATP, and LPS +ATP+ P2X7 selective inhibitor. The effects of these treatments on P2X7 receptor activity were measured through Luminex protein assay. Last, to test whether receptor stimulation was related to P2RX7 expression, relative mRNA levels of P2RX7 were quantified with real-time quantitative polymerase chain reaction. RESULTS: Several associations between the P2RX7 diplotypes and LPS-stimulated blood chemokine/cytokine levels were found between the LAP and HUC populations (P < 0.05). P2X7 activation resulted in statistically significant differences in IL-1β and IL-12p40 concentrations for both subject populations. The relative P2RX7 mRNA levels increased significantly after addition of its inhibitor for both LAP and HUC populations. CONCLUSIONS: This study detected an association between P2RX7 functional diplotypes and in vitro immune response of whole blood from subjects with LAP. In addition, we found that inhibition of the activated P2X7 receptor leads to increased P2RX7 mRNA levels, suggesting a feedback loop (ClinicalTrials.gov NCT01330719). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that P2RX7 functional diplotypes are associated with LAP and their in vitro immune response to bacteria. Ongoing studies to uncover the mechanistic link between P2RX7 and LAP phenotypes could lead to the development of preventive approaches for susceptible subjects. SN - 2380-0852 UR - https://www.unboundmedicine.com/medline/citation/31319038/Associations_of_P2RX7_Functional_Diplotypes_with_Localized_Aggressive_Periodontitis L2 - http://journals.sagepub.com/doi/full/10.1177/2380084419863789?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -