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Cytokine. 2018 Mar;103:142-149. doi: 10.1016/j.cyto.2017.09.022. Epub 2017 Sep 30.

CCR5Δ32 (rs333) polymorphism is associated with decreased risk of chronic and aggressive periodontitis: A case-control analysis based in disease resistance and susceptibility phenotypes.

Author information

1
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil; Department of Conservative Dentistry, School of Dentistry, University of Chile, Santiago, Chile.
2
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
3
Department of Periodontics, Dentistry School of University of Ribeirão Preto, Ribeirão Preto, Brazil.
4
Department of Biological and Allied Health Sciences, Sacred Heart University, Bauru, Brazil.
5
Department of Endodontics, University of Texas School of Dentistry at Houston, United States.
6
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil. Electronic address: garletgp@usp.br.

Abstract

Chronic and aggressive periodontitis are infectious diseases characterized by the irreversible destruction of periodontal tissues, which is mediated by the host inflammatory immune response triggered by periodontal infection. The chemokine receptor CCR5 play an important role in disease pathogenesis, contributing to pro-inflammatory response and osteoclastogenesis. CCR5Δ32 (rs333) is a loss-of-function mutation in the CCR5 gene, which can potentially modulate the host response and, consequently periodontitis outcome. Thus, we investigated the effect of the CCR5Δ32 mutation over the risk to suffer periodontitis in a cohort of Brazilian patients (total N=699), representative of disease susceptibility (chronic periodontitis, N=197; and aggressive periodontitis, N=91) or resistance (chronic gingivitis, N=193) phenotypes, and healthy subjects (N=218). Additionally, we assayed the influence of CCR5Δ32 in the expression of the biomarkers TNFα, IL-1β, IL-10, IL-6, IFN-γ and T-bet, and key periodontal pathogens P. gingivalis, T. forsythia, and T. denticola. In the association analysis of resistant versus susceptible subjects, CCR5Δ32 mutant allele-carriers proved significantly protected against chronic (OR 0.49; 95% CI 0.29-0.83; p-value 0.01) and aggressive (OR 0.46; 95% CI 0.22-0.94; p-value 0.03) periodontitis. Further, heterozygous subjects exhibited significantly decreased expression of TNFα in periodontal tissues, pointing to a functional effect of the mutation in periodontal tissues during the progression of the disease. Conversely, no significant changes were observed in the presence or quantity of the periodontal pathogens P. gingivalis, T. forsythia, and T. denticola in the subgingival biofilm that could be attributable to the mutant genotype.

KEYWORDS:

CCR5Δ32; Inflammation; Pathogens; Periodontitis

PMID:
28969941
DOI:
10.1016/j.cyto.2017.09.022
[Indexed for MEDLINE]

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