Publications by authors named "Corinna Bruckmann"

25 Publications

  • Page 1 of 1

Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans.

J Clin Periodontol 2021 Aug 18. Epub 2021 Aug 18.

Department of Periodontology, Oral Medicine and Oral Surgery, Charité - University Medicine Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Berlin, Germany.

Aims: Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity.

Materials And Methods: Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population.

Results: In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13).

Conclusions: Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.
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http://dx.doi.org/10.1111/jcpe.13538DOI Listing
August 2021

Bacterial colonization of a power-driven water flosser during regular use. A proof-of-principle study.

Clin Exp Dent Res 2021 May 26. Epub 2021 May 26.

Faculty of Odontology, Department of Periodontology, University of Malmö, Malmö, Sweden.

Objectives: The present proof-of-principle study assessed whether daily use of a power-driven water flosser (Sonicare AirFloss; SAF) leads to bacterial colonization in the nozzle and/or the device, resulting in contaminated water-jet.

Material And Methods: In five participants, saliva samples at baseline and water-jet samples of devices used daily with bottled water for 3 weeks (test) were collected. Additionally, water-jet samples from devices used daily with bottled water extra-orally for 3 weeks (positive control) and from brand new devices (negative control), as well as samples from newly opened and 1- and 3-week opened water bottles were collected. Colony forming units (CFU) were recorded after 48 h culturing and 20 oral pathogens were assessed by polymerase chain reaction-based analysis.

Results: Distinct inter-individual differences regarding the number of detected bacteria were observed; water-jet samples of test devices included both aerobic and anaerobic bacterial species, with some similarities to the saliva sample of the user. Water-jet samples from positive control devices showed limited number of aerobic and anaerobic bacterial species, while the samples from negative control devices did not show any bacterial species. Very few aerobic bacteria were detected only in the 3-week-old bottled water samples, while samples of newly and 1-week opened water bottles did not show any bacterial growth.

Conclusions: The present proof-of-principle study showed that daily use of a power-driven water flosser for 3 weeks resulted in bacterial colonization in the nozzle and/or device with both aerobic and anaerobic, not only oral, species, that are transmitted via the water-jet.
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http://dx.doi.org/10.1002/cre2.393DOI Listing
May 2021

Effect of personality traits on the oral health-related quality of life in patients with oral lichen planus undergoing treatment.

Clin Oral Investig 2021 Apr 14;25(4):2381-2389. Epub 2020 Sep 14.

Competence Center for Empirical Research Methods, WU Vienna University of Economics and Business, Vienna, Austria.

Objectives: The aim of this study was to evaluate the relationship between personality traits and perceived treatment success in oral lichen planus.

Material And Methods: A total of 53 patients with diagnosed oral lichen planus were evaluated at the time of diagnosis and along the course of their treatment. The visual analogue scale (VAS) was used for evaluating pain and burning sensation, along with an evaluation of the oral health-related quality of life (OHIP) and the clinical severity. In order to determine the personality trait, the NEO-FFI questionnaire was applied. Data were assessed with the statistical software Stata by a multiple linear regression.

Results: A significant relationship between the two personality traits: "conscientiousness" and "extraversion" and a perceived improvement in oral lichen planus could be observed. The higher the "conscientiousness," the better the perceived oral health-related quality of life. Furthermore, "extraversion" had a significant influence on the improvement in clinical severity index (P < 0.05).

Conclusions: Personality traits, especially conscientiousness and extraversion, have a significant impact on the perception of therapeutic intervention in oral lichen planus.

Clinical Relevance: As personalized patient management is gaining importance and psychosocial factors play a significant role in mucosal diseases, the patient's psychological profile should be considered in the oral lichen planus management.
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http://dx.doi.org/10.1007/s00784-020-03561-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966219PMC
April 2021

Does the time-point of orthodontic space closure initiation after tooth extraction affect the incidence of gingival cleft development? A randomized controlled clinical trial.

J Periodontol 2020 05 17;91(5):572-581. Epub 2019 Oct 17.

Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Background: Gingival clefts (GCs) develop frequently during orthodontic space closure and may compromise the treatment outcome. This study assessed whether the time-point of orthodontic space closure initiation, after permanent tooth extraction, affects the incidence of GC.

Methods: In 25 patients requiring bilateral premolar extraction because of orthodontic reasons, one premolar, chosen at random, was extracted 8 weeks before space closure initiation ("delayed movement," DM), whereas the contralateral premolar was extracted 1 week before ("early movement," EM) ("treatment group"). Presence or absence of GC after 3 and 6 months ("time-point") was recorded and any association with various parameters (i.e., treatment group, time-point, gender, jaw, craniofacial growth, gingival biotype, buccal bone dehiscence after extraction, space closure) was statistically assessed.

Results: Twenty-one patients contributing with 26 jaws were finally included in the analysis. Overall, GCs were frequent after 3 (DM: 53.9%; EM: 69.2%) and 6 months (DM: 76.9%; EM: 88.5%). EM (P = 0.014) and larger space closure within the study period (P = 0.001) resulted in a significantly higher incidence of GC. Further, there was a tendency for GC development in the presence of buccal bone dehiscence (P = 0.052) and thin gingival biotype (P = 0.054). "Fast movers" (herein cases with a tooth movement ≥1 mm per month) developed a GC in >90% of the cases already after 3 months. "Slow movers" developed a GC in 25% and 70% after 3 months and final evaluation, respectively.

Conclusions: GC development is a frequent finding during orthodontic space closure and seems to occur more frequently with early tooth movement initiation and in "fast movers."
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http://dx.doi.org/10.1002/JPER.19-0376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317775PMC
May 2020

A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers.

Clin Epigenetics 2019 07 22;11(1):105. Epub 2019 Jul 22.

Department of Periodontology and Synoptic Dentistry, Institute for Dental and Craniofacial Sciences, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Aßmannshauser Str. 4-6, 14197, Berlin, Germany.

Background: The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking.

Results: Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1; best p = 5.5 × 10) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p = 5.9 × 10). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p = 4.0 × 10. RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p = 2.2 × 10), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1.

Conclusion: This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.
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http://dx.doi.org/10.1186/s13148-019-0697-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647091PMC
July 2019

Screening for periodontal diseases by non-dental health professionals: a protocol for a systematic review and overview of reviews.

Syst Rev 2019 02 25;8(1):61. Epub 2019 Feb 25.

Department for Evidence-based Medicine and Clinical Epidemiology, University for Continuing Education Krems (Danube University Krems), Dr. Karl Dorrek Str. 30, 3500, Krems, Austria.

Background: Periodontal diseases are responsible for a vast burden of disease globally and are associated with other severe illnesses such as cardiovascular diseases or diabetes. Tests for early diagnosis of periodontal diseases and effective treatments are available. The effectiveness of screening for periodontal diseases to detect periodontal diseases at an early stage during periodic health examinations at primary care facilities, however, is unclear. The objective of this systematic review is to assess the benefits and risks of screening for periodontal diseases in adults during the periodic health examinations.

Methods: We will use two methodological approaches: (1) a systematic review to assess the effectiveness and risk of harms of screening for periodontal diseases during periodic health examinations and (2) an overview of systematic reviews to determine the effectiveness of treatment approaches for early periodontal disease. We will search electronic databases (Ovid MEDLINE, Embase.com , the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination databases, PubMed (non-MEDLINE content)) for published studies as well as sources for grey literature to detect unpublished studies. Two authors will independently screen abstracts and full texts using pre-defined eligibility criteria, select studies, extract data, and assess the risk of bias of included studies or reviews. In general, we will conduct a systematic narrative synthesis. Criteria for conducting meta-analyses were defined a priori. Our primary outcomes of interest are tooth loss, loosening of teeth, and depletion of bone tissue. Secondary outcomes are gingivitis/gum inflammation, pocket depths, dental hygiene, lifestyle modifications (e.g., smoking, alcohol, nutrition), and toothache. We consulted a panel of experts and patient representatives to prioritize these outcomes. Two investigators will assess independently the certainty of the evidence for each outcome using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

Discussion: We anticipate that our review will highlight the gaps in the available evidence about the effectiveness of screening for periodontal diseases during periodic health examinations. Implications for screening programs may be based on linked evidence about the validity of available screening tools and the effectiveness of early treatment.

Systematic Review Registration: PROSPERO CRD42017081150.
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http://dx.doi.org/10.1186/s13643-019-0977-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388477PMC
February 2019

Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci.

Eur J Hum Genet 2019 01 14;27(1):102-113. Epub 2018 Sep 14.

Department of Periodontology and Synoptic Dentistry, Institute of Health, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10, OR = 1.36, 95% CI = [1.23-1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10, OR = 1.24, 95% CI = [1.15-1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.
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http://dx.doi.org/10.1038/s41431-018-0265-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303247PMC
January 2019

Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.

Sci Rep 2018 09 12;8(1):13678. Epub 2018 Sep 12.

Charité - University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany.

Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (P < 0.05; P < 5 × 10; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02-1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05-1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.
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http://dx.doi.org/10.1038/s41598-018-31980-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135769PMC
September 2018

A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis.

J Clin Periodontol 2017 Oct 11;44(10):962-970. Epub 2017 Sep 11.

Department of Periodontology, Institute of Dental, Oral and Maxillary Medicine, Charité - University Medicine Berlin, Berlin, Germany.

Aim: The intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP.

Materials And Methods: The association of PLG candidate rs4252120 was tested in a German case-control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips. The German and Dutch sample of AgP cases (N = 851) and controls (N = 6,836) were genotyped with HumanOmni BeadChips. The North American CP sample (N = 2,681 cases, 1,823 controls) was previously genotyped on the Genome-Wide Human SNP Array 6.0. Genotypes were imputed (software Impute v2), and association tests were performed using an additive genetic model adjusting for sex and smoking.

Results: Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r = .08) was associated with both AgP (rs1247559; p = .002, odds ratio [OR] = 1.33) and CP (p = .02, OR = 1.15). That locus was also significantly associated with PLG expression in osteoblasts (p = 6.9 × 10 ).

Conclusions: Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.
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http://dx.doi.org/10.1111/jcpe.12749DOI Listing
October 2017

A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis.

Hum Mol Genet 2017 07;26(13):2577-2588

Clinic of Internal Medicine, University Clinic Schleswig-Holstein, Kiel, Germany.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. The disease is characterized by destruction of the alveolar bone due to an aberrant host inflammatory response to a dysbiotic oral microbiome. Previous genome-wide association studies (GWAS) have reported several suggestive susceptibility loci. Here, we conducted a GWAS using a German and Dutch case-control sample of aggressive periodontitis (AgP, 896 cases, 7,104 controls), a rare but highly severe and early-onset form of periodontitis, validated the associations in a German sample of severe forms of the more moderate phenotype chronic periodontitis (CP) (993 cases, 1,419 controls). Positive findings were replicated in a Turkish sample of AgP (223 cases, 564 controls). A locus at SIGLEC5 (sialic acid binding Ig-like lectin 5) and a chromosomal region downstream of the DEFA1A3 locus (defensin alpha 1-3) showed association with both disease phenotypes and were associated with periodontitis at a genome-wide significance level in the pooled samples, with P = 1.09E-08 (rs4284742,-G; OR = 1.34, 95% CI = 1.21-1.48) and P = 5.48E-10 (rs2738058,-T; OR = 1.28, 95% CI = 1.18-1.38), respectively. SIGLEC5 is expressed in various myeloid immune cells and classified as an inhibitory receptor with the potential to mediate tyrosine phosphatases SHP-1/-2 dependent signaling. Alpha defensins are antimicrobial peptides with expression in neutrophils and mucosal surfaces and a role in phagocyte-mediated host defense. This study identifies the first shared genetic risk loci of AgP and CP with genome-wide significance and highlights the role of innate and adaptive immunity in the etiology of periodontitis.
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http://dx.doi.org/10.1093/hmg/ddx151DOI Listing
July 2017

Can hyaluronan injections augment deficient papillae at implant-supported crowns in the anterior maxilla? A randomized controlled clinical trial with 6 months follow-up.

Clin Oral Implants Res 2017 Sep 5;28(9):1054-1061. Epub 2016 Jul 5.

Department of Periodontology, Faculty of Odontology, University of Malmö, Malmö, Sweden.

Objectives: The present randomized controlled trial aimed to assess the effect of hyaluronan (HY) injections to augment deficient interproximal papillae at implant-supported crowns in the anterior maxilla.

Methods: Twenty-two patients with a deficient papilla in the anterior maxilla next to an implant-supported crown were randomly assigned to receive twice either HY (test) or saline solution (control) injection. The following parameters were recorded prior to injection (baseline) and 3 and 6 months after injection: distance between the papilla tip and contact point (PT-CP), modified papilla index score (MPIS), and standard clinical periodontal parameters. Pain level after injection was recorded on a visual analogue scale (VAS). The deficient area was evaluated on clinical photographs, and the esthetic appearance was recorded on a VAS. Differences in mucosal volume were assessed after 3 months by intraoral scans. The bone level was assessed on periapical radiographs.

Results: No differences were observed between groups, neither at baseline nor at 3 and 6 months post-treatment. Mean PT-CP ranged between 1.8 mm and 2.3 mm without significant differences between groups or over time within groups; MPIS was 2 for all patients at all time points. Similarly, insignificant differences between groups or time points were observed for deficient area, gingival volume changes, bone level, and esthetic appearance. There were no differences in pain level between groups during injection, but discomfort after injection lasted longer in the test group.

Conclusions: Injection of HY adjacent to maxillary anterior implant-supported crowns did not result in any clinical conspicuous volume augmentation of deficient papillae.
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http://dx.doi.org/10.1111/clr.12917DOI Listing
September 2017

Adverse reaction after hyaluronan injection for minimally invasive papilla volume augmentation. A report on two cases.

Clin Oral Implants Res 2017 Jul 1;28(7):871-876. Epub 2016 Jun 1.

Department of Periodontology, Faculty of Odontology, University of Malmö, Malmö, Sweden.

Objectives: To report two cases of adverse reaction after mucosal hyaluronan (HY) injection around implant-supported crowns, with the aim to augment the missing interdental papilla.

Material And Methods: Two patients with single, non-neighbouring, implants in the anterior maxilla, who were treated within the frames of a randomized controlled clinical trial testing the effectiveness of HY gel injection to reconstruct missing papilla volume at single implants, presented an adverse reaction. Injection of HY was performed bilaterally using a 3-step technique: (i) creation of a reservoir in the mucosa directly above the mucogingival junction, (ii) injection into the attached gingiva/mucosa below the missing papilla, and (iii) injection 2-3 mm apically to the papilla tip. The whole-injection session was repeated once after approximately 4 weeks.

Results: Both patients presented with swelling and extreme tenderness with a burning sensation on the lip next to the injection area, after the second injection session. In one of the cases, a net-like skin discoloration (livedo reticularis) was also noted. The symptoms lasted for up to 7 days, and in both cases, symptoms resolved without any signs of skin or mucosal necrosis or any permanent damage.

Conclusion: Most likely, water attraction over time by the highly hygroscopic HY, exerted progressively an external vascular compression and at least partial occlusion of neighbouring blood vessels. An infection or an allergic reaction seems unlikely, since all symptoms gradually disappeared within a week irrespective use of antimicrobials, while an allergic reaction most likely would not have been restricted to one side.
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http://dx.doi.org/10.1111/clr.12892DOI Listing
July 2017

A root canal filling per se does not have a significant negative effect on the marginal periodontium.

J Clin Periodontol 2015 Jun 28;42(6):520-9. Epub 2015 May 28.

Division of Conservative Dentistry and Periodontology, Bernhard Gottlieb University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Aim: To evaluate the periodontal status of single-rooted endodontically treated teeth (ET), correcting for patient- and tooth-related factors.

Methods: Clinical parameters (BoP,PD,CAL) of 240 ET and 240 contralateral vital teeth (VT), before and after non-surgical periodontal treatment, were extracted retrospectively from the journals of 175 patients. Possible patient-related (age, gender, smoking status) and tooth-related (interproximal restoration, root canal filling's extent, post, tooth type) confounders were tested.

Results: At baseline, frequency of BoP at an interproximal site at ET versus VT was 70.4% versus 65.0%, respectively. The frequency of teeth with interproximal PD ≥ 5 mm and CAL ≥ 5 mm was 47.9% versus 42.9% and 54.6% versus 49.6% at ET and VT, respectively. Interproximal PD and CAL at ET versus VT were 3.86 versus 3.61 mm and 4.11 versus 3.95 mm. After correcting for tooth-related factors, no significant differences were observed between ET and VT. An improper restoration had a significant (p < 0.001) negative effect on BoP [OR 3.49 (95%CI: 1.95-6.27)], PD [36.81% (95%CI: 18.52-57.92)] and CAL [27.01% (95%CI: 12.67-43.18)]. No significant differences between ET and VT were observed regarding clinical outcome of non-surgical periodontal therapy.

Conclusions: Presence of a root canal filling per se does not have a significant negative influence on the marginal periodontium, when correcting for the quality of the interproximal restoration.
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http://dx.doi.org/10.1111/jcpe.12408DOI Listing
June 2015

Hyaluronan in non-surgical and surgical periodontal therapy: a systematic review.

J Clin Periodontol 2015 Mar 9;42(3):236-46. Epub 2015 Mar 9.

Department of Periodontology, Faculty of Odontology, University of Malmö, Malmö, Sweden; Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria.

Aim: To evaluate the effect of hyaluronan (HY) application as monotherapy or as adjunct to non-surgical and/or surgical periodontal therapy.

Methods: Literature search was performed according to PRISMA guidelines with the following main eligibility criteria: (a) English or German language; (b) pre-clinical in vivo or human controlled trials; (c) effect size of HY evaluated histologically or clinically.

Results: Two pre-clinical in vivo studies on surgical treatment and 12 clinical trials on non-surgical and/or surgical treatment were included. Most of the studies were highly heterogeneous, regarding with HY product used and application mode, and of high risk of bias, thus not allowing meta-analysis. The majority of clinical studies described a beneficial, occasionally statistically significant, effect of HY on bleeding on probing (BoP) and pocket depth (PD) reduction (2.28-19.5% and 0.2-0.9 mm, respectively), comparing to controls; no adverse effects were reported.

Conclusions: Hyaluronan application as adjunct to non-surgical and surgical periodontal treatment seems to have a beneficial, generally moderate, effect on surrogate outcome variables of periodontal inflammation, i.e., BoP and residual PD, and appears to be safe. The large heterogeneity of included studies, does not allow recommendations on the mode of application or effect size of HY as adjunct to non-surgical and surgical periodontal treatment.
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http://dx.doi.org/10.1111/jcpe.12371DOI Listing
March 2015

Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis.

Circ Cardiovasc Genet 2015 Feb 2;8(1):159-67. Epub 2014 Dec 2.

Background: Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms.

Methods And Results: In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case-control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10(-5); odds ratio, 1.27; 95% confidence interval, 1.3-1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8-0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-β regulation.

Conclusions: PLG is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-β signaling.
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http://dx.doi.org/10.1161/CIRCGENETICS.114.000554DOI Listing
February 2015

Inter- and intra-observer agreement on Miller's classification of gingival tissue recessions.

Odontology 2015 Sep 29;103(3):292-300. Epub 2014 Oct 29.

Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Sensengasse 2a, 1090, Vienna, Austria.

Miller's is the most commonly used classification of gingival tissue recessions, defined as the displacement of the soft tissue margin apical to the cemento-enamel junction. However, data on the reliability of this classification are missing so far, although reliability, which reflects the consistency of repeated measurements, is regarded as a prerequisite for judging the utility of a classification. The aim of the present study was to evaluate inter- and intra-observer agreement on Miller's classification of gingival tissue recessions. Two hundred photographs (50 of each region: maxillary/mandibular anterior/posterior teeth) of gingival tissue recessions were evaluated twice by four observers with different degrees of experience in Miller's classification, gingival phenotype, tooth shape, and identifiability of the cemento-enamel junction. The following inter- and intra-observer agreements were found: Miller's classification, 0.72 and 0.73-0.95; gingival phenotype, 0.29 and 0.45-0.58; tooth shape, 0.39 and 0.44-0.59; and identifiability of the cemento-enamel junction, 0.21 and 0.30-0.59. A higher agreement was detected for anterior teeth. Further, gingival phenotype (thin-high scalloping) significantly correlated with tooth shape (long-narrow) (ρ = 0.662, p < 0.001). Miller's classification of gingival tissue recessions was evaluated by four examiners using 200 clinical photographs and yielded substantial to almost perfect agreement, with higher agreement for anterior teeth. Although limited to photographic assessment, the present study offers the so far missing proof on the sufficient inter- and intra-observer agreement of this classification.
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http://dx.doi.org/10.1007/s10266-014-0179-9DOI Listing
September 2015

A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis.

J Clin Periodontol 2014 Dec 15;41(12):1122-31. Epub 2014 Nov 15.

Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.

Aim: Epidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.

Materials And Methods: Forty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.

Results: Variants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled  = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled  = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease.

Conclusion: The study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.
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http://dx.doi.org/10.1111/jcpe.12314DOI Listing
December 2014

Genome-wide exploration identifies sex-specific genetic effects of alleles upstream NPY to increase the risk of severe periodontitis in men.

J Clin Periodontol 2014 Dec 11;41(12):1115-21. Epub 2014 Nov 11.

Institute of Medical Informatics and Statistics, Christian-Albrechts-University Kiel, Kiel, Germany.

Aim: Periodontitis (PD) is influenced by genetic as well as lifestyle and socio-economic factors. Epidemiological studies show that men are at greater risk of severe forms of PD, suggesting interplay between sex and genetic factors. We aimed to systematically analyse patients with aggressive periodontitis (AgP) for gene-sex interactions.

Materials And Methods: Three hundred and twenty-nine German AgP cases and 983 controls were genotyped with Affymetrix 500K Arrays and were analysed by logistic regression analysis. The most significant gene-sex interaction was replicated in an independent sample of 382 German/Austrian AgP cases and 489 controls.

Results: Ten single-nucleotide polymorphisms (SNPs) in strong linkage disequilibrium (r(2)  > 0.85) upstream the gene neuropeptide Y (NPY) suggested gene-sex interaction (p < 5 × 10(-5) ). SNP rs198712 showed the strongest association in interaction with sex (p = 5.4 × 10(-6) ) with odds ratios in males and females of 1.63 and 0.69 respectively. In the replication, interaction of sex with rs198712 was verified with p = 0.022 (pooled p = 4.03 × 10(-6) ) and similar genetic effects. Analysis of chromatin elements from ENCODE data revealed tissue-specific transcription at the associated non-coding region.

Conclusion: This study is the first to observe a sexually dimorphic role of alleles at NPY in humans and support previous genome-wide findings of a role of NPY in severe PD.
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http://dx.doi.org/10.1111/jcpe.12317DOI Listing
December 2014

A ninety-year history of periodontosis: the legacy of Professor Bernhard Gottlieb.

J Periodontol 2015 Jan;86(1):1-6

Department of Oral Biology, School of Dental Medicine, Graduate School of Biomedical Sciences, Rutgers University, New Brunswick, NJ.

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http://dx.doi.org/10.1902/jop.2014.140202DOI Listing
January 2015

SLC23A1 polymorphism rs6596473 in the vitamin C transporter SVCT1 is associated with aggressive periodontitis.

J Clin Periodontol 2014 Jun;41(6):531-40

Department of Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.

Aim: Identification of variants within genes SLC23A1 and SLC23A2 coding for vitamin C transporter proteins associated with aggressive (AgP) and chronic periodontitis (CP).

Material And Methods: Employment of three independent case-control samples of AgP (I. 283 cases, 979 controls; II. 417 cases, 1912 controls; III. 164 cases, 357 controls) and one sample of CP (1359 cases, 1296 controls).

Results: Stage 1: Among the tested single-nucleotide polymorphisms (SNPs), the rare allele (RA) of rs6596473 in SLC23A1 showed nominal significant association with AgP (p = 0.026, odds ratio [OR] 1.26, and a highly similar minor allele frequency between different control panels. Stage 2: rs6596473 showed no significant association with AgP in the replication with the German and Dutch case-control samples. After pooling the German AgP populations (674 cases, 2891 controls) to significantly increase the statistical power (SP = 0.81), rs6596473 RA showed significant association with AgP prior to and upon adjustment with the covariates smoking and gender with padj  = 0.005, OR = 1.35. Stage 3: RA of rs6596473 showed no significant association with severe CP.

Conclusion: SNP rs6596473 of SLC23A1 is suggested to be associated with AgP. These results add to previous reports that vitamin C plays a role in the pathogenesis of periodontitis.
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http://dx.doi.org/10.1111/jcpe.12253DOI Listing
June 2014

Validation of reported genetic risk factors for periodontitis in a large-scale replication study.

J Clin Periodontol 2013 Jun 16;40(6):563-72. Epub 2013 Apr 16.

Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.

Aim: Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP).

Material And Methods: We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population.

Results: None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6-0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11-2.60]).

Conclusions: Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.
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http://dx.doi.org/10.1111/jcpe.12092DOI Listing
June 2013

Effects of enamel matrix derivative on proliferation/viability, migration, and expression of angiogenic factor and adhesion molecules in endothelial cells in vitro.

J Periodontol 2009 Oct;80(10):1622-30

Department of Periodontology, Bernhard Gottlieb University Clinic of Dentistry, Vienna, Austria.

Background: The aim of this study was to test in vitro the effect of enamel matrix derivative (EMD) on the proliferation/viability, migration, and expression of angiogenic factor and adhesion molecules in human umbilical vein endothelial cells (HUVECs). To date, discussions on angiogenic effects of EMD are rather controversial.

Methods: The effect of EMD on the proliferation/viability of HUVECs after 24 hours was measured using 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and direct cell counting. Cell migration was observed in an especially adapted in vitro monolayer wound-healing model. The expression of angiogenic factor angiopoietin-2 (ang-2) and adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular endothelium-selectin (E-selectin) was quantified with real-time polymerase chain reaction (PCR).

Results: The proliferation/viability of HUVECs measured in MTT assay was stimulated by 0.1 microg/ml EMD and inhibited by higher doses (50 to 100 microg/ml), but the total number of cells was not affected. Cell migration in the wound-healing assay was promoted by EMD at doses of 0.1 to 50 microg/ml and inhibited at 100 microg/ml. The highest expression level of all three tested genes (ICAM-1, E-selectin, and ang-2) was observed at 50 microg/ml EMD.

Conclusion: The results of the present in vitro study show the potential influence of EMD on the angiogenic activity of HUVECs, which may play an important role in periodontal tissue regeneration and wound healing.
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http://dx.doi.org/10.1902/jop.2009.090157DOI Listing
October 2009

Periodontal ligament and gingival fibroblast adhesion to dentin-like textured surfaces.

Biomaterials 2005 Jan;26(3):339-46

Department of Periodontology and Biomaterials, College of Dental Science, University Medical Centre Nijmegen, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.

It is known that the (micro-) structure of a substrate surface is of major influence on the growth behaviour of adherent cells. In the current study, we aimed to produce a surface that exactly mimics the structure of natural dentin, and to describe the effect of this surface on the growth behaviour of primary periodontal ligament fibroblasts (PDLF) or gingival fibroblasts (GF). First, we used scanning electron microscopy (SEM) and morphometric techniques to analyse the porous dentin structure. Then, using a template made by photolithographic techniques, cell culture dishes with similar surface structure were made. On these dishes, and on smooth controls, primary PDLF and GF were seeded and assayed up to 14 days for proliferation, alkaline phosphatase (ALP) activity, and collagen content. Also, cell morphology was observed with SEM and transmission electron microscopy (TEM). Results showed that GF showed significantly less ALP activity than PDLF. Abundant collagen fibres were only formed by GF grown on the textured surfaces. SEM assessment showed equal spreading of both cell types on smooth and textured surfaces. TEM showed a preferential deposition of ECM material in the texture porosity. From our study we can conclude that dentin-like surfaces have no negative effect on either cell type, and could be used to enhance extracellular matrix deposition in GF formation. However, considerable differences were observed between primary cells from different animals. Therefore, final efficacy of the surfaces remains to be proven in implantation experiments.
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http://dx.doi.org/10.1016/j.biomaterials.2004.02.031DOI Listing
January 2005
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