Periodontal infectogenomics: a systematic review update of associations between host genetic variants and subgingival microbial detection.

OBJECTIVE: The aim of this study was to systematically update the evidence for associations between host genetic variants and subgingival microbial detection and counts. MATERIALS AND METHODS: Following a previous systematic review (Nibali et al. J Clin Periodontol 43(11): 889-900, 15), an update of a systematic search of the literature was conducted in Ovid Medline, Embase, LILACS, and Cochrane Library for studies reporting data on host genetic variants and detection of microbes subgingivally published in the last 6 years. RESULTS: A total of 19 studies were included in the review, from an initial search of 2797 titles. Studies consisted mainly of candidate gene studies and of one genome-wide analysis. A total of 62 studies were considered for summary findings, including 43 identified in the previous systematic review of studies published up to 2015. Meta-analyses were done when appropriate including both papers in the original review and in the update. Meta-analyses revealed lack of associations between IL1 composite genotype and subgingival detection of Aggregatibacter acinomycetemcomitans, Poprhyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Prevotella intermedia. Promising evidence is emerging from other genetic variants and from sub-analyses of data from genome-association studies. Among other studies with candidate-gene, target SNPs were mainly within the IL10, IL6, IL4, IL8, IL17A, and VDR gene. CONCLUSIONS: IL1 composite genotype does not seem to be associated with subgingival microbial detection. Promising associations should be pursued by future studies, including studies employing -OMICS technologies. CLINICAL RELEVANCE: A better knowledge of which host genetic variant predispose to subgingival microbial colonization and to the development of progression of periodontal disease could potentially help to better understand periodontal disease pathogenesis and help with its management.

The Management of Drug-Influenced Gingival Enlargement.

INTRODUCTION:
Drug-influenced gingival enlargement (DIGE) is a reaction to specific medications, namely phenytoin, ciclosporin and calcium channel blockers. DIGE is encountered increasingly in clinical practice due to the widespread use of calcium channel blocker drugs particularly. Approaches to its management are discussed in this review.
Methods: Narrative review of the literature and discussion of clinical implications.
Findings: Management of DIGE involves nonsurgical treatment and may require surgical reduction of the overgrown gingival tissues. Management is complicated by the difficulties in achieving adequate plaque control, given the unfavourable contour of the enlarged gingival tissues, and the high frequency of recurrence of DIGE after surgical management. Replacing the drug involved can be very beneficial in selected cases, but the management of the underlying medical condition limits its application. The decision to replace a drug is not the responsibility of the dental practitioner, but the patient's physician may make it after consultation.
Conclusions: Management of DIGE can be challenging and may require close co-operation between the dental practitioner and a hygienist, a periodontist and the patient's physician. Long term supportive maintenance programmes need to be in place for optimal outcomes.

The alpha 7 nicotinic receptor agonist PHA-543613 hydrochloride inhibits Porphyromonas gingivalis-induced expression of interleukin-8 by oral keratinocytes.

OBJECTIVE: The alpha 7 nicotinic receptor (α7nAChR) is expressed by oral keratinocytes. α7nAChR activation mediates anti-inflammatory responses. The objective of this study was to determine if α7nAChR activation inhibited pathogen-induced interleukin-8 (IL-8) expression by oral keratinocytes. MATERIALS AND METHODS: Periodontal tissue expression of α7nAChR was determined by real-time PCR. OKF6/TERT-2 oral keratinocytes were exposed to Porphyromonas gingivalis in the presence and absence of a α7nAChR agonist (PHA-543613 hydrochloride) alone or after pre-exposure to a specific α7nAChR antagonist (α-bungarotoxin). Interleukin-8 (IL-8) expression was measured by ELISA and real-time PCR. Phosphorylation of the NF-κB p65 subunit was determined using an NF-κB p65 profiler assay and STAT-3 activation by STAT-3 in-cell ELISA. The release of ACh from oral keratinocytes in response to P. gingivalis lipopolysaccharide was determined using a GeneBLAzer M3 CHO-K1-bla cell reporter assay. RESULTS: Expression of α7nAChR mRNA was elevated in diseased periodontal tissue. PHA-543613 hydrochloride inhibited P. gingivalis-induced expression of IL-8 at the transcriptional level. This effect was abolished when cells were pre-exposed to a specific α7nAChR antagonist, α-bungarotoxin. PHA-543613 hydrochloride downregulated NF-κB signalling through reduced phosphorylation of the NF-κB p65-subunit. In addition, PHA-543613 hydrochloride promoted STAT-3 signalling by maintenance of phosphorylation. Furthermore, oral keratinocytes upregulated ACh release in response to P. gingivalis lipopolysaccharide. CONCLUSION: These data suggest that α7nAChR plays a role in regulating the innate immune responses of oral keratinocytes.

Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

OBJECTIVES: The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity. INTRODUCTION: Acetylcholine can influence the immune system via the 'cholinergic anti-inflammatory pathway'. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) on proximate immuno-regulatory cells. Activation of the α7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the α7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response. METHODS: A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the 'cholinergic anti-inflammatory pathway' in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium. CONCLUSION: The evidence suggests a functional non-neuronal 'cholinergic anti-inflammatory pathway' may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease.