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Background: The primary goal of this pilot study was to evaluate the success of a smoking cessation programme on smoking behaviour of patients with chronic periodontitis. Secondary goals were to identify the prevalence of smoking among them, predictors of motivation for smoking cessation and for successful nicotine abstinence. Methods: Smokers suffering from chronic periodontitis were offered cognitive behavioural group therapy of 10 once-weekly sessions. Smoking is reduced stepwise and complete cessation is to be achieved by the sixth session. Sociodemographic data, history of smoking and motivation for smoking cessation, subjective health status, and questionnaires on anxiety, depression, control beliefs and coping with stress were completed at study entry. Smoking behaviour was assessed at the end of the group programme and 3 months thereafter. Results: Of 469 patients with periodontitis, 59 (12.6%) were smokers; 30 (50.6%) patients participated in the smoking cessation programme. Participants smoked more cigarettes/day (P = 0.03, 95% CI: −17.9/−0.89) and subjectively assessed their health as being worse than non-participants (P = 0.09, 95% CI: −0.16/2.15). In SPQ, non-participants showed more trivialization (P = 0.014, 95% CI: 0.59/4.94). Complete data were available for 15 group participants: six patients were smoke-free after 10 weeks and five after 18 weeks (33.3%); two patients had reduced their cigarette consumption by half. At the start of the programme, less successful participants showed a tendency to higher depression in HADS (P = 0.085, 95% CI: −5.25/5.76) and were more inclined to seek substitute satisfaction (P = 0.034, 95% CI: 3.24/11.23). Conclusion: The rate of success in this study was comparable with other studies. More research with larger samples is needed for confirming these observations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Safety and efficacy of glycine powder air-polishing (GPAP) in removing subgingival biofilm have been previously demonstrated. The hypothesis that GPAP results in less gingival erosion than sodium bicarbonate air-polishing (SBAP) or hand-instrumentation was assessed. MATERIAL AND METHODS: In each of 10 patients, eight teeth with a residual probing depth of at least 5 mm following initial periodontal therapy were randomly assigned to the following interventions: GPAP (test), SBAP (positive control), hand-instrumentation (positive control), or no treatment (negative control). In each group, gingival biopsies were taken immediately after instrumentation and one 14 days later. Damaged gingival epithelium (GE) was assessed by light microscopy and quantified by a histological score (values 1-4). Differences between groups were evaluated using the marginal homogeneity test. RESULTS: GPAP resulted in minor erosions of the GE (scores 1 and 2), whereas positive control specimens displayed moderate to severe erosions (scores 2-4). Differences between GPAP and positive controls were significant (p<0.05). Fourteen days following instrumentation GE under assessment was found to be intact in all groups. CONCLUSION: The data indicated that GPAP results in less gingival erosion than SBAP or hand instrumentation, further supporting the safety of this new debridement technique. [ABSTRACT FROM AUTHOR]

Beikler T, Peters U, Prior K, Ehmke B, Flemmig TF. Sequence variations inrgpAandrgpBofPorphyromonas gingivalisin periodontitis. J Periodont Res 2005; 40: 193–198.© Blackwell Munksgaard 2005The aim of the present study was to determine sequence variations in the active centre of the Arg-X-specific protease encoding genesrgpAandrgpBof clinicalPorphyromonas gingivalisisolates and to analyse their prevalence in periodontitis patients before and 3 months after mechanical periodontal therapy.Genetic diversity at nucleotides 281, 283, 286 and 331 has been shown to result in amino acid substitutions in the catalytic domain of RgpA and RgpB that affect the substrate specificity and thus may influence the efficacy of Arg-X-protease specific inhibitors.Sequence analysis ofrgpAandrgpBgenes in clinicalP. gingivalisstrains isolated from subgingival plaque samples of 82 periodontitis patients before and 3 months after mechanical supra- and subgingival debridement was performed.No specific variation within thergpAsequence was observed. However, thergpBsequence in the region of the active centre showed five differentrgpBgenotypes, which were named NYPN, NSSN, NSSK, NYPK and DYPN according to the derived amino acid substitution.Porphyromonas gingivalisgenotype NYPN was detected in 27 patients (32.9%) before and in 8 patients (9.8%) after therapy, NSSN in 26 (31.7%) and 10 (12.2%), NSSK in 22 (26.8%) and 2 (2.4%), NYPK in 5 (6.2%) and 1 (1.2%), and DYPN in 1 patient (1.2%) and 0 patients (0%), respectively. Only one patient (1.2%) harboured twoP. gingivalis rgpBgenotypes (NSSK/NYPN) before treatment; these were no longer detected after therapy.The results indicate that fivergpBgenotypes are maintained in natural populations ofP. gingivalis.These data may be of importance with regard to the development of specificrgpBinhibitors. [ABSTRACT FROM AUTHOR]

Introduction: The aim was to evaluate the suitability of paper points or endodontic nickel-titanium files to sample microorganisms for in vivo investigation of endodontic microbiota by 16S ribosomal DNA (rDNA) sequencing., Methods: Forty-five patients presenting clinical and radiological signs of apical periodontitis were recruited for sampling, giving their written informed consent. Glide paths were assessed using C-Pilot Files and K-Files under electronic root canal length control under aseptic conditions. Microbial samples were taken from 84 root canals in duplicate, the first sample with a sterile paper point (size 15), the second with a sterile file (size 20/.06). After DNA extraction, the hypervariable region V4 of the bacterial 16 S rRNA gene was amplified and sequenced (Illumina MiSeq). Sequencing data were trimmed with Cutadapt and exact amplicon sequence variants generated by DADA2. Taxonomy was assigned based on the Human Oral Microbiome Database (eHOMD). Statistical analysis of diversity parameters comprised Wilcoxon signed-rank tests and permutational analysis of variance (PERMANOVA). Compositional differences were evaluated by differential abundance analysis (DESeq2). Microbial contamination during the sampling process and analysis were evaluated., Results: Concerning alpha diversity, richness and dissimilarity differed nonsignificantly between paper point and instrument samples (P > .05), whereas a significant difference was observed in the Shannon index (P < .05). Regarding beta diversity, paper point and instrument samples presented with similar microbial community compositions (P = 1.0, PERMANOVA). Paper point controls contained significantly higher proportions of Pseudomonadales (P < .05)., Conclusions: Paper point and endodontic instrument sampling generate valid specimens for 16S rDNA community profiling. Endodontic instrument sampling is easier to execute and, therefore, could be the technique of choice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To help fill the knowledge gaps regarding the long-term effectiveness of peri-implantitis therapy, this retrospective study of soldiers with treated severe periodontitis (stage III gen. / IV) who had been undergoing adherent SPT for at least 20 years aimed to determine the frequency of peri-implantitis and patient-related risk factors for this, as well as the 10-year survival rates of dental implants under peri-implantitis therapy., Materials and Methods: The observation period was between 1993 and 2023. All patients were referred by their military dentists for specialist dental training and underwent systematic periodontal therapy. A multi-stage peri-implantitis treatment concept was used., Results: In 86 (31%) of 276 patients (total treatment time 23.6 ± 2.8 years, 53.1 ± 20.4 SPT sessions), 296 implant restorations were performed to close gaps or lengthen rows of teeth. In 29 (33%) of the implant patients, peri-implantitis developed on 25% of the implants. As a result, 11% of all implants were lost within 10 years due to peri-implantitis. Peri-implantitis led to implant loss in 59% of affected patients and 45% of implants. The survival time of implants lost later was 8.4 ± 6.2 years. Peri-implantitis and implant loss rates increased statistically significantly in stage IV periodontitis as well as in heavy smokers. Patients with implant loss and peri-implantitis had received systemic antibiotics due to periodontitis recurrence statistically significantly more frequently than patients without peri-implantitis and without implants during the ≥ 20-year SPT (p 0.05)., Conclusions: Based on the present results, the early extraction of teeth during SPT in patients with treated generalised periodontitis stage III and stage IV plus replacement with implants is not advantageous.

Aims: To explore the influence of gender on periodontal treatment outcomes in a dataset of eight RCTs conducted in Brazil, United States, and Germany., Methods: Clinical parameters were compared between men and women with stages III/IV grades B/C generalized periodontitis at baseline and 1-year post-therapy, including scaling and root planing with or without antibiotics., Results: Data from 1042 patients were analyzed. Men presented a tendency towards higher probing depth (p = .07, effect size = 0.11) and clinical attachment level (CAL) than women at baseline (p = .01, effect size = 0.16). Males also presented statistically significantly lower CAL gain at sites with CAL of 4-6 mm at 1-year post-therapy (p = .001, effect size = 0.20). Among patients with Grade B periodontitis who took antibiotics, a higher frequency of women achieved the endpoint for treatment (i.e., ≤4 sites PD ≥5 mm) at 1 year than men (p < .05, effect size = 0.12)., Conclusion: Men enrolled in RCTs showed a slightly inferior clinical response to periodontal therapy in a limited number of sub-analyses when compared to women. These small differences did not appear to be clinically relevant. Although gender did not dictate the clinical response to periodontal treatment in this population, our findings suggest that future research should continue to explore this topic., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota's composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy's efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment., Methods: Subgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes., Results: We identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14-1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00-1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes., Conclusions: The shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles. Video Abstract., (© 2024. The Author(s).)

Aim: An excessively activated or dysregulated complement system has been proven to be a vital contributor to the pathogenesis of periodontitis. It has been previously hypothesized that inhibiting the activity of complement component C5 by targeting the C5a receptor is a powerful candidate for treating periodontitis. Here, we apply the drug target instrumental variable (IV) approach to investigate the therapeutic effect of genetically proxied inhibition of C5 on periodontitis., Method: In our primary analysis, we used 26 independent 'cis' single nucleotide polymorphisms as IVs from the vicinity of the encoding locus of C5 that are associated with plasma C5 levels. In a secondary analysis, we assess the validity of our primary findings, exploring the involvement of alternative downstream biomarkers, interleukin 17 (IL-17), interleukin 1β (IL-1β), and tumor necrosis factor (TNF). Summary statistics of plasma levels (C5, IL-17, IL-1β, and TNF) were obtained from a genome-wide association study (GWAS) of 35,559 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis., Results: In our primary approach, inhibiting C5 reduced the risk of periodontitis (Odds ratio 0.89 per 1 standard deviation reduction in C5; 95% confidence Interval 0.80-0.98, p value=0.022). Our secondary analysis suggests an involvement of IL-17 within the potential causal pathway, but was inconclusive for other biomarkers., Conclusions: The findings from our study suggest that C5 inhibition may reduce the risk of periodontitis, prioritizing C5 inhibitors as a potential adjunctive therapeutic intervention in this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alayash, Baumeister, Holtfreter, Kocher, Baurecht, Ehmke, Reckelkamm and Nolde.)

Aim: Evidence from a Phase IIa trial showed that a complement C3-targeted drug reduced gingival inflammation in patients with gingivitis. Using drug-target Mendelian randomization (MR), we investigated whether genetically proxied C3 inhibition alters the risk of periodontitis., Materials and Methods: We used multiple 'cis' instruments from the vicinity of the encoding loci of C3. Instrument selection was restricted to the drug target encoding loci (chromosome 19; 6,677,715-6,730,573 (GRCh37/hg19)). We selected three uncorrelated single-nucleotide polymorphisms (rs141552034, rs145406915, rs11569479) that were associated with serum C3 levels (p value <1 × 10 -4 ) from a genome-wide association study (GWAS) of 5368 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis to estimate the odds ratio (OR) of the genetically proxied inhibition of C3 in relation to periodontitis., Results: MR analysis revealed that the inhibition of C3 reduces the odds of periodontitis (OR 0.91 per 1 standard deviation reduction in C3; 95% confidence interval 0.87-0.96, p value = .0003)., Conclusions: Findings from our MR analysis suggest a potential protective effect of C3 blockade against periodontitis., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objectives: Periodontitis (PD) can cause systematic inflammation and is associated with various metabolic processes in the body. However, robust serum markers for these relationships are still lacking. This study aims to identify novel circulating inflammation-related proteins associated with PD using targeted proteomics., Materials and Methods: We used population-based, cross-sectional data from 619 participants of the Polish Longitudinal University Study (Bialystok PLUS). Mean pocket probing depth (mPPD) and proportion of bleeding on probing (pBOP) served as exposure variables. Fifty-two inflammation-related proteins were measured using the Olink Target 96 Cardiovascular III and the Olink Target 96 Immune Response panels. Associations between periodontal measures and proteins were tested using covariate-adjusted linear regression models., Results: At a false discovery rate of < 0.05, we identified associations of mPPD and pBOP with platelet-endothelial cell adhesion molecule-1 (PECAM-1) and tripartite motif-containing protein 21 (TRIM21)., Conclusion: This study revealed novel associations between PD and serum levels of PECAM-1 and TRIM21. Our results suggest that these proteins might be affected by molecular processes that take place in the inflamed periodontium., Clinical Relevance: Novel associations of PECAM-1 and TRIM21 with PD indicate promising serum markers for understanding the disease's pathophysiological processes and call for further biomedical investigations., (© 2023. The Author(s).)

Aim: Assessment of treatment response after systemic amoxicillin/metronidazole adjunctive to subgingival instrumentation (SI) according to stages and grades of the 2018 classification of periodontal diseases., Materials and Methods: We carried out exploratory re-analysis of the placebo-controlled, multi-centre ABPARO trial (52; 45/60 years of age; 205 males, 114 active smokers). Patients were randomized to SI with systemic amoxicillin 500 mg/metronidazole 400 mg (three times a day for 7 days, n = 205; ANTI) or placebo (n = 200; PLAC) and maintenance therapy every 3 months. Patients were reclassified according to the 2018 classification (stage/extent/grade). Treatment effect was the percentage of sites per patient with new attachment loss ≥1.3 mm (PSAL ≥ 1.3 mm) at 27.5 months post-baseline/randomization., Results: All patients were assigned according to the stage (n = 49 localized stage III, n = 206 generalized stage III, n = 150 stage IV). Because of missing radiographs, only 222 patients were assigned to grades (n = 73 B, n = 149 C). Treatment (PLAC/ANTI) resulted in PSAL ≥ 1.3 mm (median; lower/upper quartile) in localized stage III (PLAC: 5.7; 3.3/8.4% vs. ANTI: 4.9; 3.0/8.3%; p = .749), generalized stage III (8.0; 4.5/14.3% vs. 4.7; 2.4/9.0%; p < .001), stage IV (8.5; 5.1/14.4% vs. 5.7; 3.3/10.6%; p = .008), grade B (4.4; 2.4/6.7% vs. 3.6; 1.9/4.7%; p = .151) and grade C (9.4; 5.3/14.3% vs. 4.8; 2.5/9.4%; p < .001)., Conclusions: In generalized periodontitis stage III/grade C, a clinically relevant lower percentage of disease progression after adjunctive systemic amoxicillin/metronidazole was observed compared to placebo (PLAC: 9.7; 5.8/14.3% vs. ANTI: 4.7; 2.4/9.0%; p < .001)., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Aim: To explore whether adjunctive antibiotics can relevantly influence long-term microbiota changes in stage III-IV periodontitis patients., Materials and Methods: This is a secondary analysis of a randomized clinical trial on periodontal therapy with adjunctive 500 mg amoxicillin and 400 mg metronidazole or placebo thrice daily for 7 days. Subgingival plaque samples were taken before and 2, 8, 14 and 26 months after mechanical therapy. The V4-hypervariable region of the 16S rRNA gene was sequenced with Illumina MiSeq 250 base pair paired-end reads. Changes at the ribosomal sequence variant (RSV) level, diversity and subgingival-microbial dysbiosis index (SMDI) were explored with a negative binomial regression model and non-parametric tests., Results: Overall, 50.2% of all raw reads summed up to 72 RSVs (3.0%) that were generated from 163 stage III-IV periodontitis patients. Of those, 16 RSVs, including Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans, changed significantly over 26 months because of adjunctive systemic antibiotics. SMDI decreased significantly more in the antibiotic group at all timepoints, whereas the 2-month differences in alpha and beta diversity between groups were not significant at 8 and 14 months, respectively., Conclusions: Mechanical periodontal therapy with adjunctive antibiotics induced a relevant and long-term sustainable change towards an oral microbiome more associated with oral health., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objectives: Observational studies suggested an inverse association between physical activity and periodontitis. However, observational studies might be subject to unobserved confounding and reverse causation bias. We conducted an instrumental variable study to strengthen the evidence on the relationship between physical activity and periodontitis., Materials and Methods: We used genetic variants associated with self-reported and accelerometer-assessed physical activity in 377,234 and 91,084 UK Biobank participants, respectively, as instruments. For these instruments, genetic associations with periodontitis were obtained from 17,353 cases and 28,210 controls in the GeneLifestyle Interactions in Dental Endpoints consortium., Results: We found no evidence for effects of self-reported moderate-to-vigorous physical activity, self-reported vigorous physical activity, accelerometry "average accelerations," and "fraction of accelerations > 425 milli-gravities" on periodontitis. For example, the odds ratio for self-reported moderate-to-vigorous physical activity was 1.07 (95% credible interval: 0.87; 1.34) in Causal Analysis using Summary Effect Estimates. We conducted sensitivity analyses to rule out weak instrument bias and correlated horizontal pleiotropy., Conclusions: The study does not support an effect of physical activity on the risk of periodontitis., Clinical Relevance: This study provides little evidence that recommending physical activity would help prevent periodontitis., (© 2023. The Author(s).)

Aim: Interleukin 6 (IL-6) is considered to play a role in the dysbiotic host response in the development of periodontitis. While the inhibition of the IL-6 receptor using monoclonal antibodies is a well-established therapy for some diseases, so far, its potential benefit in patients with periodontitis has not been examined. We tested the association of genetically proxied downregulation of IL-6 signaling with periodontitis to explore whether downregulation of IL-6 signaling could represent a viable treatment target for periodontitis., Materials and Methods: As proxies for IL-6 signaling downregulation, we selected 52 genetic variants in close vicinity of the gene encoding IL-6 receptor that were associated with lower circulating C-reactive protein (CRP) levels in a genome-wide association study (GWAS) of 575 531 participants of European ancestry from the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Associations with periodontitis were tested with inverse-variance weighted Mendelian randomization in a study of 17 353 cases and 28 210 controls of European descent in the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) consortium. In addition, the effect of CRP reduction independent of the IL-6 pathway was assessed., Results: Genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis (odds ratio (OR) = 0.81 per 1-unit decrement in log-CRP levels; 95% confidence interval (CI): [0.66;0.99]; P = 0.0497). Genetically proxied reduction of CRP independent of the IL-6 pathway had a similar effect (OR = 0.81; 95% CI: [0.68; 0.98]; P = 0.0296)., Conclusion: In conclusion, genetically proxied downregulation of IL-6 signaling was associated with lower odds of periodontitis and CRP might be a causal target for the effect of IL-6 on the risk of periodontitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nolde, Alayash, Reckelkamm, Kocher, Ehmke, Holtfreter, Baurecht, Georgakis and Baumeister.)

Background: The purpose of the study was to examine the association between total body bone mineral density (BMD) and periodontitis using Mendelian randomization (MR) analysis., Methods and Materials: We used 81 single nucleotide polymorphisms (SNPs) associated with BMD at a p-value of < 5 × 10 -8 from a genome-wide association study (GWAS) of 66,628 individuals of European descent. The GWAS for periodontitis was derived from a meta-analysis of seven cohort studies that included 17,353 cases and 28,210 controls of European ancestry., Results: MR showed no association between BMD and periodontitis (odds ratio per standard deviation increment in genetically predicted BMD = 1.00; 95% confidence interval: 0.92-1.08). Leave-one-out analyses and pleiotropy-robust methods did not indicate any bias., Conclusions: The MR study provided no evidence that BMD might be causally linked to periodontitis. Hence it may be concluded as the key finding that BMD depletion does not increase the risk of periodontitis., (© 2022 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Background: Circulating levels of interleukin-17 (IL-17) are associated with the presence and severity of periodontitis. However, whether IL-17 is causal for disease development is unknown. We investigated the effect of genetically proxied IL-17 on periodontitis using instrumental variable analysis., Methods: We identified 12 genetic variants from genome-wide association study (GWAS) of 7760 European descent individuals, used these variants as instrumental variables for IL-17, and linked them to a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Generalized weighted least squares analysis accounted for linkage disequilibrium of variants., Results: We found an inverse association of genetically proxied IL-17 and periodontitis (odds ratio, 0.84; 95% confidence interval: 0.75-0.94; p = 0.003), which was corroborated after sensitivity analysis for horizontal pleiotropy., Conclusion: The findings suggest that IL-17 protects against initial periodontitis., (© 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Aim: To investigate the effect of genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) on the risk of periodontitis., Materials and Methods: Genetic instruments were selected from the vicinity of TNFR superfamily member 1A (TNFRSF1A) gene (chromosome 12; base pairs 6,437,923-6,451,280 as per GRCh37 assembly) based on their association with C-reactive protein (N= 575,531). Summary statistics of these variants were obtained from a genome-wide association study (GWAS) of 17,353 periodontitis cases and 28,210 controls to estimate the effect of TNFR1 inhibition on periodontitis using a fixed-effects inverse method., Results: Considering rs1800693 as an instrument, we found no effect of TNFR1 inhibition on periodontitis risk (Odds ratio (OR) scaled per standard deviation increment in CRP: 1.57, 95% confidence interval (CI): 0.38;6.46). Similar results were derived from a secondary analysis that used three variants (rs767455, rs4149570, and rs4149577) to index TNFR1 inhibition., Conclusions: We found no evidence of a potential efficacy of TNFR1 inhibition on periodontitis risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alayash, Baumeister, Holtfreter, Kocher, Baurecht, Ehmke, Reckelkamm and Nolde.)

Aim: Epidemiological and pre-clinical studies suggest a chemoprotective role of lipid-lowering agents in periodontitis. We tested the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), Niemann-Pick C1-Like 1 (NPC1L1) and proprotein convertase subtilisin/kexin type 9 (PCSK9) with periodontitis., Materials and Methods: Genetic variants in HMGCR, NCP1L1 and PCSK9 associated with low-density lipoprotein (LDL) cholesterol in a genome-wide association study (GWAS) meta-analysis (N = 188,578) were used to proxy therapeutic inhibition of HMGCR, NPC1L1 and PCSK9. For these genetic variants, associations with periodontitis were obtained from GWAS of 17,353 cases and 28,210 controls in the GeneLifestyle Interactions in Dental Endpoints consortium. Generalized weighted least squares analysis accounted for linkage disequilibrium of genotypes to derive pooled estimates., Results: While genetically proxied HMGCR inhibition equivalent to 1 mmol/L reduction in LDL was not associated with odds of periodontitis (odds ratio [OR] = 0.92 [95% confidence interval [CI]: 0.73; 1.16]; p = .4905; false discovery rate [FDR] = 0.4905), genetically proxied NPC1L1 (OR = 0.53 [95% CI: 0.35; 0.81]; p = .0038; FDR = 0.0077) and PCSK9 (OR = 0.84 [95% CI: 0.74; 0.95]; p = .0051; FDR = 0.0077) inhibition lowered the odds of periodontitis., Conclusions: Genetically proxied inhibition of NCP1L1 and PCSK9 was associated with lower odds of periodontitis., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Twenty five-hydroxy vitamin D (25OHD) levels have been proposed to protect against periodontitis based on in vitro and observational studies but evidence from long-term randomized controlled trials (RCTs) is lacking. This study tested whether genetically proxied 25OHD is associated with periodontitis using Mendelian randomization (MR)., Methods: Genetic variants strongly associated with 25OHD in a genome-wide association study (GWAS) of 417,580 participants of European ancestry were used as instrumental variables, and linked to GWAS summary data of 17,353 periodontitis cases and 28,210 controls. In addition to the main analysis using an inverse variance weighted (IVW) model, we applied additional robust methods to control for pleiotropy. We also undertook sensitivity analyses excluding single nucleotide polymorphisms (SNPs) used as instruments with potential pleiotropic effects and used a second 25OHD GWAS for replication. We identified 288 SNPs to be genome-wide significant for 25OHD, explaining 7.0% of the variance of 25OHD levels and providing ≥90% power to detect an odds ratio (OR) of ≤ 0.97., Results: MR analysis suggested that a 1 standard deviation increase in natural log-transformed 25OHD was not associated with periodontitis risk (IVW OR = 1.04; 95% confidence interval (CI): 0.97-1.12; P-value = 0.297). The robust models, replication, and sensitivity analyses were coherent with the primary analysis., Conclusions: Collectively, our findings suggest that 25OHD levels are unlikely to have a substantial effect on the risk of periodontitis, but large long-term RCTs are needed to derive definitive evidence on the causal role of 25OHD in periodontitis., (© 2022 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)