Yvonne Jockel-Schneider

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

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.

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

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-&bgr; 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-&bgr; signaling.

On the relationship between gingival biotypes and supracrestal gingival height, crown form and papilla height

OBJECTIVES To determine the association between gingival biotypes and supracrestal gingival height (primary aim) and its relation to crown shape and papilla height (secondary aim). MATERIALS AND METHODS Eighty adult subjects were evaluated in this study. Based on the transparency of a periodontal probe through the buccal gingival margin, 38 subjects comprised the thin biotype group and 42 subjects comprised the thick biotype group, respectively. Three different parameters were clinically assessed: supracrestal gingival height (SGH) by bone sounding, crown width/crown length ratio and papilla height. RESULTS No statistical difference (P > 0.05) was detected neither for the correlation between different biotypes (thick/thin) and SGH nor for the association of biotypes and crown width/crown length ratio. Papilla height was only significantly increased (P ≤ 0.05) in the area of teeth no. 21/22 for the thin periodontal biotype. Intra-examiner deviation was found to be very low for all clinical parameters (percentile agreement > 95%). CONCLUSIONS Within the limits of this study, we found that in young Caucasians (i) soft tissue dimensions seem to be similar between biotypes (ii) and the traditional hypothesis that a thick gingiva merges with broad-short crown shape and flat papillae and a thin gingiva with a narrow-long crown shape and high scalloping, may be questionable.

Arterial stiffness and pulse wave reflection are increased in patients suffering from severe periodontitis.

Aim This single blind cross-sectional study compared the vascular health of subjects suffering from severe chronic periodontitis, severe aggressive periodontitis and periodontal healthy controls by evaluating pulse wave velocity (PWV), augmentation index (AIx) and pulse pressure amplification (PPA). Material and Methods In a total of 158 subjects, 92 suffering from severe periodontitis and 66 matched periodontal healthy controls, PWV, AIx, central and peripheral blood pressure were recorded using an oscillometric device (Arteriograph). Results Subjects suffering from severe chronic or aggressive periodontitis exhibited significantly higher PWV (p = 0.00004), higher AIx (p = 0.0049) and lower PPA (p = 0.028) than matched periodontal healthy controls. Conclusions The results of this study confirm the association between periodontal inflammation and increased cardiovascular risk shown by impaired vascular health in case of severe periodontitis. As impaired vascular health is a common finding in patients suffering from severe periodontal disease a concomitant routine cardiovascular evaluation may be advised.

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

Abstract 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.

Regular consumption of Lactobacillus reuteri‐containing lozenges reduces pregnancy gingivitis: an RCT

Abstract Aim This randomized controlled trial assessed the impact of Lactobacillus reuteri on pregnancy gingivitis in healthy women. Materials and Methods Forty‐five healthy women (24 test/21 placebo) with pregnancy gingivitis in the third trimester of pregnancy were enrolled. At baseline Gingival Index (GI) and Plaque Index (PlI) were assessed at the Ramfjord teeth and venous blood taken for TNF‐α analysis. Subsequently participants were randomly provided with lozenges to be consumed 2 × daily until birth (approx. 7 weeks) containing ≥108 CFU L. reuteri ATCC PTA 5289 and ≥108 CFU L. reuteri DSM 17938 (test) or being devoid of L. reuteri (placebo). Within 2 days after birth recording of GI, PlI and blood sampling were repeated. Results At baseline, mean GI and mean PlI did not differ significantly between both groups. In the test group mean TNF‐α serum level was significantly (p < 0.02) lower than in the placebo group. At reevaluation, mean GI and mean PlI of the test group were both significantly (p < 0.0001) lower than in the placebo group. Mean TNF‐α serum level did no longer differ significantly between the groups. Conclusions The consumption of L. reuteri lozenges may be a useful adjunct in the control of pregnancy gingivitis.

Impact of the Daily Use of a Microcrystal Hydroxyapatite Dentifrice on De Novo Plaque Formation and Clinical/Microbiological Parameters of Periodontal Health. A Randomized Trial

Aim This 12-week prospective, randomized, double-blind, two-center trial evaluated the impact of a microcrystalline zinc hydroxyapatite (mHA) dentifrice on plaque formation rate (PFR) in chronic periodontitis patients. We hypothesized that mHA precipitates cause delayed plaque development when compared to a fluoridated control (AmF/SnF2), and therefore would improve periodontal health. Material & Methods At baseline and after 4 and 12 weeks, PFR and other clinical and microbiological parameters were recorded. Seventy periodontitis patients received a mHA or AmF/SnF2 dentifrice as daily oral care without hygiene instructions. Four weeks after baseline, participants received full mouth debridement and continued using the dentifrices for another 8 weeks. Results Primary outcome PFR did not change statistically significantly from baseline to weeks 4 and 12, neither in mHA (n = 33; 51.7±17.2% vs. 48.5±16.65% vs. 48.4±19.9%) nor in AmF/SnF2-group (n = 34; 52.3±17.5% vs. 52.5±21.3% vs. 46.1±21.8%). Secondary clinical parameters such as plaque control record, gingival index, bleeding on probing, and pocket probing depth improved, but between-group differences were not statistically significant. Microbiological analyses showed similar slight decreases in colony-forming units in both groups. Conclusion In patients with mild-to-moderate periodontitis, periodontal therapy and use of a mHA-or AmF/SnF2 dentifrice without instructions induced comparable improvements in periodontal health but did not significantly reduce the PFR. Trial Registration ClincalTrials.gov NCT02697539

Early wound healing and patient morbidity after single-incision vs. trap-door graft harvesting from the palate—a clinical study

ObjectivesThe aim of this study is to compare wound healing and patient pain perception of single-incision (single-incision, modified single-incision) and trap-door surgical techniques to harvest subepithelial connective tissue grafts from the palate.Material and methodsThirty-six patients were selected for root coverage procedures with subepithelial connective tissue grafts and randomly assigned to two single-incision groups or a trap-door group (n = 12/group). One week after surgery, a modified early-wound healing index (EHI), patient pain and painkiller intake were recorded. Follow-up was performed until complete epithelialization was achieved.ResultsSingle-incision techniques showed significantly improved early healing over trap-door approaches. Specifically, the mean EHI was 2.50 ± 1.14 for single-incision techniques, as compared to 3.33 ± 1.30 for trap door. The incidence of secondary healing was significantly lower in the single-incision groups. Concomitantly, the cumulative dosage and duration of painkiller intake were significantly reduced, as compared to the trap-door group.ConclusionWithin the limits of this trial, single-incision techniques can lead to improved early healing and reduced patient pain after subepithelial connective tissue graft harvesting than trap-door techniques.Clinical relevanceAvoiding trap-door incisions for harvesting of connective tissue grafts may reduce patient morbidity.

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

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 (PAgP-Ger < 0.05; PCAD < 5 × 10−8; 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.

Wild‐type isolates of Porphyromonas gingivalis derived from periodontitis patients display major variability in platelet activation

In vitro studies revealed that Porphyromonas gingivalis (Pg), a pathogen intimately associated with the onset and progression of periodontitis, is able to activate platelets, thus linking periodontal inflammation with the endangerment of vascular health. As wild-type Pg strains are characterized by major genetic heterogeneity, the commonness of platelet-activating Pg strains in periodontitis patients is unknown as of yet. Therefore, this study evaluated the platelet activation capacity of wild-type Pg isolates sampled from patients with aggressive periodontitis. METHODS Extent and velocity of platelet aggregation were determined by light transmission aggregometry. Platelet surface expression of P-selectin was measured by flow cytometry, activation of p38 MAP kinase, and protein kinase C by Western blot using phospho-specific antibodies. RESULTS Pg isolates displayed high variability regarding extent and velocity of platelet activation, as well as the involved activating pathways. Corresponding results were observed for platelet P-selectin expression, activation of p38 MAP kinase, or protein kinase C. Inhibitors of platelet immune receptor FcγRIIA and protease-activated receptors revealed several, diverging pathways of activation. Some isolates induced platelet aggregation even in the presence of potent therapeutical platelet inhibitors. CONCLUSIONS Chronic bacteremia involving specific, platelet-activating Pg strains may constitute a substantial hazard for the integrity of cardiovascular health.