Transferrin receptor 2 mitigates periodontitis-driven alveolar bone loss.

Periodontitis is associated with significant alveolar bone loss. Patients with iron overload suffer more frequently from periodontitis, however, the underlying mechanisms remain largely elusive. Here, we investigated the role of transferrin receptor 2 (Tfr2), one of the main regulators of iron homeostasis, in the pathogenesis of periodontitis and the dental phenotype under basal conditions in mice. As Tfr2 suppresses osteoclastogenesis, we hypothesized that deficiency of Tfr2 may exacerbate periodontitis-induced bone loss. Mice lacking Tfr2 (Tfr2-/- ) and wild-type (Tfr2+/+ ) littermates were challenged with experimental periodontitis. Mandibles and maxillae were collected for microcomputed tomography and histology analyses. Osteoclast cultures from Tfr2+/+ and Tfr2-/- mice were established and analyzed for differentiation efficiency, by performing messenger RNA expression and protein signaling pathways. After 8 days, Tfr2-deficient mice revealed a more severe course of periodontitis paralleled by higher immune cell infiltration and a higher histological inflammation index than Tfr2+/+ mice. Moreover, Tfr2-deficient mice lost more alveolar bone compared to Tfr2+/+ littermates, an effect that was only partially iron-dependent. Histological analysis revealed a higher number of osteoclasts in the alveolar bone of Tfr2-deficient mice. In line, Tfr2-deficient osteoclastic differentiation ex vivo was faster and more efficient as reflected by a higher number of osteoclasts, a higher expression of osteoclast markers, and an increased resorptive activity. Mechanistically, Tfr2-deficient osteoclasts showed a higher p38-MAPK signaling and inhibition of p38-MAPK signaling in Tfr2-deficient cells reverted osteoclast formation to Tfr2+/+ levels. Taken together, our data indicate that Tfr2 modulates the inflammatory response in periodontitis thereby mitigating effects on alveolar bone loss.

Psychopathologies and socioeconomic status as risk indicators for periodontitis: a survey-based investigation in German dental practices.

OBJECTIVES: Periodontitis is a highly prevalent multifactorial disease associated with various mental disorders. However, study results about this association are still contradictory. One methodological reason could be the neglect of potential confounders, such as socioeconomic factors or mental comorbidity. Our study examined a wide range of potential psychosocial risk indicators to identify those with relevant associations to periodontitis. MATERIALS AND METHODS: In a cross-sectional study, 111 patients with periodontitis (PERIO) (> 30% teeth with approximal attachment loss ≥ 5 mm) and 110 patients without periodontitis (NON-PERIO) were recruited in four dental practices in Germany. Clinical attachment loss, pocket depth, plaque, bleeding on probing, and DMFT were measured. Psychopathologic symptoms and socioeconomic status were recorded using self-report questionnaires (DAS, PHQ-8, GAD-7, CTS, SCOFF, AUDIT, FTND, SSS-8, SES). RESULTS: The PERIO group reported significantly lower socioeconomic status (Cohen's d = 0.49) and higher psychopathological symptom burden than the NON-PERIO regarding dental anxiety (d = 0.86) and avoidance behavior, nicotine dependency (d = 0.84), depressiveness (d = 0.46), general anxiety (d = 0.45), somatic symptoms (d = 0.42), and childhood traumatization (d = 0.34). No significant group differences existed for alcohol abuse and eating disorders. Dental anxiety was the strongest predictor of periodontitis and showed significant correlations with other psychopathologies and social status. CONCLUSIONS: Out of all psychosocial factors, socioeconomic status and dental anxiety showed the greatest association with periodontitis. CLINICAL RELEVANCE: Dentists should encourage socially disadvantaged and dentally anxious patients in the utilization of prevention and dental care. Furthermore, physicians and psychotherapists can contribute to the early detection of dental anxiety, oral diseases, and avoidance behavior.

Impact of 0.1% octenidine mouthwash on plaque re-growth in healthy adults: a multi-center phase 3 randomized clinical trial.

OBJECTIVES: To investigate plaque inhibition of 0.1% octenidine mouthwash (OCT) vs. placebo over 5 days in the absence of mechanical plaque control. MATERIALS AND METHODS: For this randomized, placebo-controlled, double-blind, parallel group, multi-center phase 3 study, 201 healthy adults were recruited. After baseline recording of plaque index (PI) and gingival index (GI), collection of salivary samples, and dental prophylaxis, subjects were randomly assigned to OCT or placebo mouthwash in a 3:1 ratio. Rinsing was performed twice daily for 30 s. Colony forming units in saliva were determined before and after the first rinse. At day 5, PI, GI, and tooth discoloration index (DI) were assessed. Non-parametric van Elteren tests were applied with a significance level of p < 0.05. RESULTS: Treatment with OCT inhibited plaque formation more than treatment with placebo (PI: 0.36 vs. 1.29; p < 0.0001). OCT reduced GI (0.04 vs. placebo 0.00; p = 0.003) and salivary bacterial counts (2.73 vs. placebo 0.24 lgCFU/ml; p < 0.0001). Tooth discoloration was slightly higher under OCT (DI: 0.25 vs. placebo 0.00; p = 0.0011). Mild tongue staining and dysgeusia occurred. CONCLUSIONS: OCT 0.1% mouthwash inhibits plaque formation over 5 days. It therefore can be recommended when regular oral hygiene is temporarily compromised. CLINICAL RELEVANCE: When individual plaque control is compromised, rinsing with octenidine mouthwash is recommended to maintain healthy oral conditions while side effects are limited.

Massive data analyses show negative impact of type 1 and 2 diabetes on the outcome of periodontal treatment.

OBJECTIVES: The aim was to evaluate the impact of diabetes on the outcome of periodontal treatment based on massive data analyses. MATERIALS AND METHODS: Data originated from the database of a major German National Health Insurance. Patients who underwent periodontal treatment were allocated to four groups according to their medical condition: type 1 diabetes (D1), type 2 diabetes with the intake of oral anti-diabetics (D2M), type 2 diabetes without the intake of oral anti-diabetics (D2), and a control group without diabetes (ND). Four-year Kaplan-Meier survival analyses on the patient level and multivariate regression analyses were conducted for tooth extraction. RESULTS: Of 415,718 patients, 4139 matched the criteria for D1, 22,430 for D2M, and 23,576 for D2. At 4 years, the cumulative survival rate (no extraction) was 51.7% in the D1 group, 54.0% in the D2M group, and 57.7% in the D2 group. The ND control group had a significantly higher survival rate of 65.9% (P < 0.0001). In the multivariate analyses, both diabetes types were significantly associated with further tooth loss after periodontal treatment. CONCLUSIONS: The diagnosis of diabetes type 1 or 2 seems to be associated with a higher risk of tooth loss after periodontal treatment. CLINICAL RELEVANCE: The long-term prognosis of teeth in diabetes patients should be judged carefully.

Effect of toothpaste containing amine fluoride and stannous chloride on the reduction of dental plaque and gingival inflammation. A randomized controlled 12-week home-use study.

OBJECTIVES: This single-centre, controlled, randomized, double-blinded clinical study in parallel groups was performed to assess the efficacy of an experimental toothpaste on plaque and gingivitis. METHODS: In adult subjects with gingivitis, amine fluoride/stannous chloride toothpaste (test) and monofluorophosphate toothpaste (control) were applied twice daily by regular toothbrushing at home. Evaluations of plaque index (PI), gingival index (GI), modified sulcus bleeding index (mSBI) and safety took place at baseline and after 3 and 12 weeks of study product use. After study completion, all subjects received a dental prophylaxis. A descriptive statistical analysis included means and standard deviations. Unpaired t tests compared index reductions between groups at a significance level of 0.05. RESULTS: Intention-to-treat analysis included 240 out of 241 subjects. Baseline mean PI was reduced by 0.87 ± 0.35 in the test group and by 0.65 ± 0.41 in the control group. Within-group differences and between-group differences in index reduction were statistically significant (P < 0.001). Mean GI and mSBI were reduced significantly over time (P < 0.001) with no clinically meaningful differences between groups. CONCLUSIONS: Both toothpastes reduced plaque and gingivitis statistically significant and clinically meaningful over 12 weeks. Compared to the control toothpaste, application of the amine fluoride/stannous chloride toothpaste led to a clinically meaningful and more pronounced plaque reduction.

Tooth loss after periodontal treatment-Mining an insurance database.

OBJECTIVES: The aim of this study was to evaluate tooth loss after periodontal treatment. METHODS: The data was collected from the digital database of a major German national health insurance company. Periodontal treatment was the intervention in the treatment group. Kaplan-Meier survival analyses on the patient level with the primary outcome extraction were carried out over four years. A control group without treatment was matched and analysed. Differences were tested with the Log-Rank-test. Extraction incidences were calculated over a matched observation period six years before and four years after treatment for both treatment and control group. RESULTS: A total of 415,718 periodontal treatments could be traced. Focussing on the outcome "extraction", the cumulative four-year survival rate was 63.8% after periodontal treatment. The matched control group without periodontal treatment showed a survival rate of 72.5%. These differences were significant (p < 0.0001). The extraction incidence over time was higher in a four-year period after periodontal treatment compared to a six-year period before periodontal treatment. CONCLUSIONS: The outcome of periodontal treatment was acceptable. In about two thirds of the patients, extractions could be completely avoided within a four year period after treatment. CLINICAL SIGNIFICANCE STATEMENT: This study within the German national health insurance system shows that extractions were not observed after periodontal treatment in the majority of cases. Although periodontitis is a chronic disease, patients suffering from periodontitis have a considerable chance to prevent further tooth loss.

Obesity alters composition and diversity of the oral microbiota in patients with type 2 diabetes mellitus independently of glycemic control.

BACKGROUND AND OBJECTIVE: The involvement of the oral microbiota as a possible link between periodontitis, type 2 diabetes mellitus and obesity is still not well understood. The objective of the study was to investigate if glycemic control and obesity play a role in modulating the composition and diversity of the oral microbial ecology. MATERIAL AND METHODS: A cohort of patients with type 2 diabetes mellitus (n = 18) was recruited. Participants demonstrating improved glycemic control after 3 months (n = 6) were included in a second examination. A full mouth examination was performed to estimate periodontitis severity followed by sample collection (subgingival plaque and saliva). Generation of large sequence libraries was performed using the high-throughput Illumina MiSeq sequencing platform. RESULTS: The majority of participants (94.4%, n = 17) presented with moderate or severe forms of periodontitis. Differences in microbial composition and diversity between obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) groups were statistically significant. Cross-sectional and longitudinal approaches failed to reveal statistically significant associations between HbA1c level and species composition or diversity. CONCLUSIONS: Obesity was significantly associated with the oral microbial composition. The impact of glycemic control on oral microbiota, however, could not be assured statistically.

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

OBJECTIVES: This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. MATERIALS AND METHODS: Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. RESULTS: At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63-5.44 log10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69-4.22 log10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. CONCLUSIONS: Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. CLINICAL RELEVANCE: Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552).

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

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.

Oral Health and Quality of Life in Old Age: A Cross-Sectional Pilot Project in Germany and Poland.

BACKGROUND: The process of ageing influences all dimensions of social life and personal well-being, but the influence of health on different dimensions of quality of life (QoL) among the elderly is rarely examined. OBJECTIVES: The aim of the pilot study is to test the feasibility of a comprehensive study design to evaluate general and dental health as well as QoL in a bi-national sample. In addition, this pilot study should allow for the exploration of potential interactions between QoL, socioeconomic, health and oral health variables. MATERIAL AND METHODS: Individuals aged 64 years and older (n = 100) from university dental clinics of the Wroclaw Medical University, Poland (n = 50) and of the University Hospital in Dresden, Germany (n = 50) were examined. The oral health status of participants was assessed by clinical examination. Socio-demographic, environmental and general health status were evaluated during the medical interview. General quality of life (GQoL) was assessed by an overall question with a visual analogue scale (VAS) from -5 (worst) to +5 (best). Health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL) were measured with the EQ-5D and OHIP-14 questionnaires. Statistical analyses comprised Pearson's c2 test, Wilcoxon test, linear regression model for statistical analysis and different multivariate linear regression analyses. RESULTS: For the GQoL-VAS-Score the results for QoL measurements were 1.22 ± 2.62 (x± SD), for EQ-5D-Score 7.45 ± 2.25 (x± SD), and for OHIP-14-ADD-Score 11.04 ± 13.56 (x± SD). Differences between Polish and German populations were observed. CONCLUSIONS: The study design proved to be feasible for a senior population. The overall GQoL question, EQ-5D and OHIP-14 were regarded as appropriate instruments. Subjective and objective (oral) health measures showed differences between Germany and Poland. For methodological reasons, these differences are not generalizable, but of value for study hypotheses in larger samples.

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-ß 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-ß signaling.

Tooth staining potential of experimental amine fluoride/stannous fluoride mouth rinse formulations-a randomized crossover forced staining study.

OBJECTIVES: It was the aim to investigate experimental mouth rinses concerning their tooth and tongue staining potential using the standardized short-term forced staining model. MATERIALS AND METHODS: A single centre, clinically controlled, randomized, investigator-blinded study was conducted in a crossover design. In healthy dental students, three experimental AmF/SnF2 (A, B, C) mouth rinses and a phenolic/essential oil rinse (D) were compared to a water control (E). Four treatment days consisted of eight hourly rinses with mouth rinse and black tea. Mechanical oral hygiene was ceased. At the fifth day, tooth and tongue staining indices were recorded. Between treatment periods, a 10-day washout phase was performed. RESULTS: Twenty-eight participants entered and completed the study. All mouth rinses including the water control led to tooth and tongue staining. Most tooth staining occurred after rinsing with test rinse A, followed by B, D, C and E. Statistically significant differences existed between products A and C, D, and E. Most tongue staining happened in group B, followed by A, D, C and E (not statistically significant). CONCLUSION: Within the limitations of the model, mouth rinse C has a promising potential of causing less tooth discoloration than other AmF/SnF2 rinses. C is highly recommended to be investigated in further long-term clinical studies on its in vivo staining potential and antiplaque efficacy. CLINICAL RELEVANCE: This forced staining study has proven that one of the experimental AmF/SnF2 rinses leads to less staining than the other experimental AmF/SnF2 rinses. These experimental results have to be confirmed by further clinical investigations.

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

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.

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

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.

Analysis of gastrin-releasing peptide gene and gastrin-releasing peptide receptor gene in patients with agoraphobia.

A gastrin-releasing peptide receptor (GRPR) knock-out mouse model provided evidence that the gastrin-releasing peptide (GRP) and its neural circuitry operate as a negative feedback-loop regulating fear, suggesting a novel candidate mechanism contributing to individual differences in fear-conditioning and associated psychiatric disorders such as agoraphobia with/without panic disorder. Studies in humans, however, provided inconclusive evidence on the association of GRP and GRPR variations in agoraphobia with/without panic disorder. Based on these findings, we investigated whether GRP and GRPR variants are associated with agoraphobia. Mental disorders were assessed via the Munich-Composite International Diagnostic Interview (M-CIDI) in 95 patients with agoraphobia with/without panic disorder and 119 controls without any mental disorders. A complete sequence analysis of GRP and GRPR was performed in all participants. We found no association of 16 GRP and 7 GRPR variants with agoraphobia with/without panic disorder.

Clinical outcomes after treatment of periodontal intrabony defects with nanocrystalline hydroxyapatite (Ostim) or enamel matrix derivatives (Emdogain): a randomized controlled clinical trial.

INTRODUCTION: Periodontitis is an inflammatory process in response to dental biofilm and leads to periodontal tissue destruction. The aim of this study was the comparison of outcomes using either an enamel matrix derivative (EMD) or a nanocrystalline hydroxyapatite (NHA) in regenerative periodontal therapy after 6 and 12 months. METHODS: Using a parallel group, prospective randomized study design, we enrolled 19 patients in each group. The primary outcome was bone fill after 12 months. Attachment gain, probing pocket depth (PPD) reduction, and recession were secondary variables. Additionally, early wound healing and adverse events were assessed. Data analysis included test of noninferiority of NHA group (test) compared to EMD group (reference) in bone fill. Differences in means of secondary variables were compared by paired t-test, frequency data by exact χ(2) test. RESULTS: Both groups showed significant bone fill, reduction of PPD, increase in recession, and gain of attachment after 6 and 12 months. No significant differences between groups were found at any time point. Adverse events were comparable between both groups with a tendency of more complaints in the NHA group. CONCLUSION: The clinical outcomes were similar in both groups. EMD could have some advantage compared to NHA regarding patients comfort and adverse events. The trial is registered with ClinicalTrials.gov NCT00757159.

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

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.

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.