CCR5 Delta 32 (rs333) polymorphism is associated with decreased risk of chronic and aggressive periodontitis: A case-control analysis based in disease resistance and susceptibility phenotypes

Author(s)

Cavalla, Franco ^{[1, 2]} ; Biguetti, Claudia C. ^[1] ; Dionisio, Thiago J. ^[1] ; Azevedo, Michelle C. S. ^[1] ; Martins, Jr., Walter ^[3] ; Santos, Carlos F. ^[1] ; Trombone, Ana Paula F. ^[4] ; Silva, Renato M. ^[5] ; Letra, Ariadne ^[5] ; Garlet, Gustavo P. ^[1]

Affiliation

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Sao Paulo - Brazil

^[2] Univ Chile, Sch Dent, Dept Conservat Dent, Santiago - Chile

^[3] Univ Ribeirao Preto, Sch Dent, Dept Periodont, Ribeirao Preto - Brazil

^[4] Univ Sagrado Coracao, Dept Biol & Allied Hlth Sci, Bauru - Brazil

^[5] Univ Texas Sch Dent Houston, Dept Endodont, Houston, TX - USA

• Document type: Journal article
• Source: CYTOKINE; v. 103, p. 142-149, MAR 2018.
• Web of Science Citations: 5

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. CCR5 Delta 32 (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 CCR5 Delta 32 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 CCR5 Delta 32 in the expression of the biomarkers TNFa, IL-10, IL-6, IFN-y and T-bet, and key periodontal pathogens P. gingivalis, T. forsythia, and T. denticola. In the association analysis of resistant versus susceptible subjects, CCR5 Delta 32 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 TNFa 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. (AU)

• FAPESP's process: 14/03276-0 - Influence of genetic polymorphisms in the colonization/recolonization patterns in chronic periodontitis patients
• Grantee: Ian Franco Cavalla Ruiz
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/17886-4 - Influence of genetic polymorphisms in the patterns of bacterial colonization and recolonization in chornic periodontitis patients
• Grantee: Gustavo Pompermaier Garlet
• Support Opportunities: Regular Research Grants