A novel three-dimensional quantitative assessment method for abnormal root morphology of the maxillary premolars in vivo on cone-beam computed tomography.

BACKGROUND: Previous studies have described and recorded abnormal root morphology; however, most of these studies were based on two-dimensional periapical or panoramic radiographs, and only a few studies have quantified it. We aimed to combine two-dimensional periapical radiographs and three-dimensional cone-beam computed tomography (CBCT) to conduct qualitative judgments and quantitative analyses of normal and conical roots, and explore the clinical diagnostic method of normal and conical roots based on intraoral radiographs and CBCT. METHODS: The conical root was identified visually on periapical radiographs as the clinical gold standard. All teeth were divided into the cone-rooted teeth (CRT) or normal-rooted teeth (NRT) groups. Furthermore, differences in root length (RL), root surface area (RSA), and root volume (RV) of conical and normal roots in the maxillary premolars on CBCT were compared. Receiver operator characteristic curves were generated, and the area under the curve (AUC) and cut-off values were calculated to evaluate the diagnostic value of RV, RSA, RV/RL, and RSA/RL. RESULTS: The RSAs of NRT and CRT were 236.88 ± 27.93 mm2 and 207.98 ± 27.80 mm2, respectively (P = 0.000). The mean RV in the CRT group was lower than that in the NRT group, and the difference was statistically significant (253.40 ± 41.98 mm3 vs. 316.93 ± 49.89 mm3, P = 0.000). The RSA and RV of conical roots in single root premolars were 12.29% and 19.33% less than those of normal roots, respectively. The AUC values of RSA/RL and RV/RL were 0.87 and 0.89, respectively, and the best cut-off values were 19.61 for RSA/RL (if RSA/RL was < 19.61, the teeth were considered CRT) and 24.05 for RV/RL (if RV/RL was < 24.05, the teeth were considered CRT). CONCLUSIONS: CBCT has significant diagnostic value in the clinical evaluation of conical roots. RSA/RL and RV/RL were the best parameters with the largest AUC and high sensitivity and specificity.

Platelets as inflammatory mediators in a murine model of periodontitis.

AIM: To investigate the role of platelets during the development of ligature-induced experimental periodontitis in mice. MATERIALS AND METHODS: Experimental periodontitis was induced by placement of sterilized 5-0 cotton ligatures around the maxillary and mandibular second molars of C57BL/6 wild-type mice. Flow cytometry was used to analyse platelet activation and platelet-leucocyte aggregate formation, and histologic analysis was used to evaluate inflammation and localization of platelets and leucocytes in periodontal tissues during the development of experimental periodontitis and in experimental periodontitis with and without antiplatelet drug treatment. RESULTS: Experimental periodontitis induced platelet activation and platelet-leucocyte interaction. Platelets and leucocytes gradually infiltrated in inflammatory gingival tissues during the development of experimental periodontitis. The inhibition of platelet activation via drug therapy led to significant inhibition of leucocyte migration and marked reduction in periodontal inflammation. CONCLUSION: This study revealed that platelets are critical for inflammation and tissue injury in periodontitis and serve as mediators of inflammation in periodontal tissue.

Association of CYP1A1 rs1048943 variant with aggressive periodontitis and its interaction with hyperlipidemia on the periodontal status.

BACKGROUND AND OBJECTIVE: CYP1A1 rs1048943 polymorphism was reported to be correlated with periodontitis; however, its association with aggressive periodontitis (AgP) has not yet been investigated. The aim of the study was to investigate the association between the CYP1A1 gene rs1048943 variant with generalized aggressive periodontitis (GAgP) and platelet activation and analyse whether its interaction with hyperlipidemia affects periodontal status in a Chinese population. METHODS: A case-control study of 224 GAgP patients and 139 healthy controls was conducted. The clinical parameters of probing depth (PD), attachment loss (AL) and bleeding index (BI) were recorded. Platelet count (PLT), platelet distribution width (PDW), platelet large cell ratio (PLCR), mean platelet volume (MPV), serum total cholesterol (TC), triacylglycerol (TG), high and low-density lipoprotein (HDL and LDL) were also measured. The CYP1A1 rs1048943 SNP was genotyped by time-of-flight mass spectrometry. Logistic and linear regression models were used to measure correlation. RESULTS: The CYP1A1 rs1048943 AG/GG genotype was associated with GAgP (OR = 1.56, 95%CI: 1.01, 2.42), PD, AL and decreased PDW, PLCR and MPV after adjustment for covariates. Gene-lipid interactions were found between CYP1A1 rs1048943 and HDL for PD (Pinteraction  = 0.0033), BI (Pinteraction  = 0.0311) and AL (Pinteraction  = 0.0141) and between CYP1A1 rs1048943 and LDL for PD (Pinteraction  = 0.013) among patients with GAgP. CONCLUSION: The G allele of the CYP1A1 rs1048943 gene was associated with GAgP, periodontal status and platelet-related inflammation status in a Chinese population. Hyperlipidemia could modulate the effect of CYP1A1 rs1048943 on the periodontal status of GAgP.

The role of platelets in inflammatory immune responses in generalized aggressive periodontitis.

AIM: To investigate the relationship between inflammatory markers and platelet size in generalized aggressive periodontitis (GAgP). MATERIAL AND METHODS: Periodontal, inflammatory and platelet indices were compared between 59 GAgP patients and 59 healthy subjects. Gingival biopsies from five patients and five healthy subjects were examined by immunohistochemistry and electron microscopy. Changes in patient periodontal and platelet indices were re-evaluated at 3 months after periodontal therapy. RESULTS: Platelet size was decreased significantly in GAgP patients compared to healthy subjects (p ≤ 0.003). Weak negative correlations between platelet size and periodontal parameters were found in GAgP patients (p ≤ 0.025). Platelet aggregates and adhesion to the endothelium or leucocytes were found in venules and connective tissues of gingival biopsies from GAgP patients. Mean platelet volume (MPV) and platelet large cell ratio increased after periodontal therapy in GAgP patients (p ≤ 0.038). The increase in MPV was related to the decrease in bleeding index in GAgP patients after periodontal therapy (p < 0.001; r = 0.357). CONCLUSION: Platelet size was reduced in GAgP patients compared to healthy controls, possibly due to the consumption of large platelets at sites of periodontal inflammation. Platelets may be involved in host responses to periodontal infection in GAgP.

[Association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis].

OBJECTIVE: To investigate the potential association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis, which may provide benefits for diagnosis and treatment of aggressive periodontitis. METHODS: A total of 353 patients with aggressive periodontitis (group AgP) and 125 matched controls (group HP) were recruited in the study. Genotyping of FADS1 rs174537 and serum biochemical indexes were tested at the study's start. The relationships between the levels of TP, GLB, ALB, A/G and genotyping were analyzed. RESULTS: (1) The detection rate of allele G in group AgP was higher than that in group HP(68.1% vs. 61.2%, P=0.046,OR=1.35,95% CI 1.00-1.83); the detection rate of genotype GG in group AgP was higher than in group HP(45.5% vs. 34.4%,P=0.029, OR=1.60, 95% CI 1.05-2.44). (2) In group AgP, the patients with GG genotype exhibited significantly lower TP, GLB than the patients with GT+TT genotype [(77.08 ± 7.88) g/L vs. (79.00 ± 4.66) g/L, P=0.007; (28.17 ± 7.63) g/L vs.(29.88 ± 3.49) g/L,P=0.007) and the higher A/G(1.72 ± 0.22 vs.1.67 ± 0.22, P=0.040), but there was no significant difference in ALB between the patients with GG genotype and the patients with GT+TT genotype. In group HP, there were no significant differences in TP, GLB, A/G and ALB between individuals with genotype GT+TT and with genotype GG. (3)Compared with individuals with genotype GT+TT in group HP, the AgP patients with genotype GT+TT exhibited significantly higher TP, GLB [(79.00 ± 4.66) g/L vs. (75.20 ± 4.53) g/L, P<0.01; (29.88 ± 3.49) g/L vs.(26.55 ± 2.94) g/L, P<0.01) and the lower A/G(1.67 ± 0.22 vs. 1.88 ± 0.30, P<0.01), but there was no significant difference in ALB. There were no significant differences in TP, GLB, A/G and ALB the between the AgP patients with genotype GG and the healthy subjects with the same genotype either. CONCLUSION: FADS1 rs174537 polymorphism is associated with aggressive periodontitis. The patients with genotype GG in group AgP had relatively lower TP,GLB and higher A/G. Genotype GG might be a risk indicator for aggressive periodontitis by reducing host defense capability and contributing to inflammatory response in the occurrence and development of aggressive periodontitis.

Mean platelet volume as an inflammatory marker in patients with severe periodontitis.

Periodontitis has become the leading cause of tooth loss in adults, and the host's immunologic and inflammatory response to the bacteria can lead to periodontal destruction. In patients with periodontitis, platelets possess an increased activation status compared with platelets from healthy controls. Mean platelet volume (MPV) has been considered an important index of platelet activity and an inflammatory marker in many infectious diseases. The present study investigated the relationship between MPV and disease activity in subjects with severe periodontitis. Forty-five patients with periodontitis and 45 age and sex-matched healthy subjects were enrolled into the study. All subjects received periodontal and hematological examinations. The periodontitis patients were administered active periodontal treatment (APT). At baseline, a statistically significant decrease in MPV was noted in patients with periodontitis (9.73 ± 1.06 fL) compared with healthy controls (10.24 ± 1.07 fL). At 1 month post-APT, MPV was substantially increased (10.11 ± 1.04 fL). Positive correlation was found between increase of MPV and decrease of periodontal probing depth after treatment(r = 0.377; p = 0.014). In conclusion, the decrease of MPV was related to the severe periodontal inflammation, and the value inversed shift after APT. MPV might reflect the disease activity of periodontitis.

[Clinical effect of different sequences of debridement-antibiotic therapy in treatment of severe chronic periodontitis].

OBJECTIVE: To evaluate the feasibility of full-mouth debridement (subgingival scaling and root planning, SRP) by 2 times within 1 week and compare the clinical effects of different sequences of debridement-antibiotic usage in patients with severe chronic periodontitis (CP). METHODS: A double-blinded, placebo-controlled, randomized clinical trial was conducted in 30 severe CP patients (14 males and 16 females, 40.5 ± 8.4 years old on average from 35 to 60) receiving 3 different sequences of debridement-antibiotictherapy: Group A, antibiotic usage (metronidazole, MTZ, 0.2 g, tid, 7 d; amoxicillin, AMX 0.5 g, tid, 7 d) was started together with SRP (completed by 2 times in 7 d); Group B, antibiotic usage (MTZ 0.2 g, tid, 7 d; AMX 0.5 g, tid, 7 d) was started 1 d after SRP(completed by 2 times in 7 d); Group C, SRP alone[probing depth (PD), bleeding index (BI) and tooth mobility] was examined. The average full-mouth probing depth, the average full-mouth proximal probing depth (pPD), the percentage of sites with PD>5 mm (PD>5 mm%), the percentage of sites with proximal PD>5 mm (pPD>5 mm%), the average bleeding index (BI) and the percentage of sites with bleeding on probing (BOP%) were calculated. Clinical examinations were performed at baseline and 2 months post therapy. RESULTS: (1) Compared with baseline conditions, all the subjects showed clinical improvements in all the parameters evaluated 2 months post therapy, P<0.05. (2) Significant difference were observed in the average PD changes between Group A [(2.15 ± 0.42) mm], Group B [(1.76 ± 0.29) mm] and Group C [(1.57 ± 0.33) mm], P<0.05. No significant difference was observed in the average PD changes between Group B and Group C, P=0.354. Significant differences were observed in the average pPD changes between Group A [(2.45 ± 0.43)mm] and Group C[(1.90 ± 0.48) mm], P<0.05. No significant difference was observed in BI and BOP% changes between Group A,Group B and Group C. CONCLUSION: For patients with severe chronic periodontitis, it is safe and feasible to receive full-mouth SRP by 2 times within 1 week. The short-term (2 months) advantages in PD changes are observed in patients receiving SRP and antibiotic usage at the same time comparing with patients using antibiotics after SRP or SRP alone.

[Predictive model for post-treatment tooth loss of patients with aggressive periodontitis].

OBJECTIVE: To establish a predictive model for long-term tooth loss of patients with aggressive periodontitis (AgP) after periodontal treatment. METHODS: Patients diagnosed as AgP in Department of Periodontology, Peking University School and Hospital of Stomatology, who were re-evaluated 3 to 11 years after periodontal treatment were enrolled (n=85). Logistic regression was performed to select background, periodontal and radiographic factors which were related to long-term post-treatment tooth loss. A predictive model was built and analyzed by receiver operator characteristic (ROC) curve. RESULTS: After periodontal treatment, 55 teeth from 22 patients lost further. High prevalence of baseline bone loss, root abnormality, and residual severe bleeding sites, as well as poor compliance to maintenance were detected as risk factors in the predictive model. ROC analysis found the sensitivity and specificity of the model could reach up to 80% simultaneously. CONCLUSION: Predictive model for post-treatment tooth loss of patients with AgP is an important adjunct in clinical practice.

Comparison of the inflammatory states of serum and gingival crevicular fluid in periodontitis patients with or without type 2 diabetes mellitus.

Background/purpose:There is a two-way relationship between periodontitis and type 2 diabetes mellitus. This study aimed to compare the inflammatory states in serum and gingival crevicular fluid (GCF) in periodontitis patients with or without type 2 diabetes mellitus (T2DM) and healthy subjects. Materials and methods: 20 subjects were systematic and periodontal healthy (H group), 40 subjects were with periodontitis (CP group), and other 40 were with periodontitis and type 2 diabetes mellitus (DC group). Fasting blood glucose (FBG) and HbA1c was tested. GCF and serum level of interleukin (IL) -17, visfatin, receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL)/osteoprotegerin (OPG) ratio were measured. Results: The GCF volume, total amount of IL-17, vastatin, RANKL/OPG ratio in GCF and their concentrations in serum were higher (P < 0.05) in CP and DC groups than in H group, which were also higher (P < 0.05) in DC group than in CP group except for visfatin in GCF and IL-17 in serum. At sample sites of PD ≤ 3 mm, GCF volume, IL-17, visfatin and RANKL/OPG ratio in DC and CP groups were higher (P < 0.05) than that in H group, which were also higher in DC group than in CP group either with PD ≤ 3 mm or PD > 3 mm. Inflammatory state in GCF was positively correlated to systemic inflammation, and both of them were positively correlated to FBG. Conclusion: Moderate and severe periodontitis aggravated systemic inflammation. T2DM together with periodontitis resulted in more severe systemic inflammation. The positive correlation between the periodontal and systemic inflammation and their association with FBG indicated an inflammatory link between periodontitis and T2DM.

Preliminary study on the involvement of platelets in mouse experimental periodontitis.

Background/purpose: Although some studies have taken an interest in the participation of platelets in periodontitis, so far, we know very little about the roles of platelets in periodontitis. The objective of this study is to explore the involvement of platelets in the development of experimental periodontitis in mice. Materials and methods: Twenty C57BL/6 male mice were used for this study. Experimental periodontitis models of mice were constructed by ligating for 1, 3, 7, and 14 days, respectively. Morphological changes in the alveolar bone were assessed by micro-computed tomography (Micro-CT). The gingival crevicular fluid samples of ligation sites were collected and stained by immunocytochemistry. Immunohistochemistry was used to detect platelets infiltration in gingival tissues of mice. Results: The results of Micro-CT showed that with the extension of ligation time, alveolar bone resorption increased, suggesting that the experimental periodontitis models were established. Immunochemical staining showed that there were almost no platelets in the gingival crevicular fluid of mice ligated for 1 and 3 days. And at 7 and 14 days of ligation, a large number of platelets were present in the gingival crevicular fluid and formed complexes with neutrophils. And with the extension of ligation time, the extent of platelet infiltration increased in mice gingival tissues. Conclusion: Platelets were infiltrated increasedly in the gingival sulcus and gingival tissues following the experimental time, and may participate in the development of mouse experimental periodontitis.

Multilevel Analysis of Non-surgical Periodontal Treatment of Patients with Generalised Aggressive Periodontitis.

OBJECTIVE: To investigate various factors affecting the clinical outcome of nonsurgical periodontal treatment and evaluate the treatment effects of adjunctive amoxicillin and metronidazole (AMX + MET) in patients with generalised aggressive periodontitis (GAgP). METHODS: Forty-two patients with GAgP were recruited and randomly assigned to three groups: scaling and root planing (SRP) only, AMX + MET after SRP, and AMX + MET during SRP. The patients were assessed every 2 months post-therapy. Periodontal clinical and subgingival microbiological parameters were analysed at baseline and 6 months post-therapy. The impacts of different covariates on pocket probing depth (PD) reduction were evaluated. RESULTS: A multilevel analysis revealed that 58% of the variability in PD reduction was attributed to site-level parameters, 27.3% to patient-level parameters and 18.7% to tooth-level parameters. Greater PD reduction can be expected at initially deeper PD sites and sites with intrabony defects, and in patients with adjunctive use of AMX + MET. Persistent Tannerella forsythia infection and tooth mobility after treatment were negatively associated with PD reduction. CONCLUSION: The clinical outcomes of nonsurgical periodontal treatment were mainly influenced by site-level parameters, and adjunctive use of AMX + MET can lead to better clinical results in patients with GAgP in a short time.

Clinical evaluation of ultrasonic subgingival debridement versus ultrasonic subgingival scaling combined with manual root planing in the treatment of periodontitis: study protocol for a randomized controlled trial.

BACKGROUND: Periodontal diseases are regarded as the most common diseases of mankind. The prevalence rate of periodontal disease assumes a clear growth tendency, increasing by 57.3% from 1990 to 2010. Thereby, effective periodontal therapy is still a long-term task and a difficult problem. The goals of periodontal therapy are to eliminate the infectious and inflammatory processes of periodontal diseases. Root planing, in order to eliminate the "infected cementum," has been an important step in the treatment of periodontitis since the 1970s. However, along with the understanding of the effects of endotoxin on the root surface, the necessity of manual root planing has been gradually queried. Ultrasonic instruments, which are more recent innovations, would not remove the cementum excessively, and are also more time-saving and labor-saving compared to using hand instruments. Hence, an increasing number of dentists prefer to do scaling with ultrasonic instruments only. However, the necessity of root planing remains emphasized in the international mainstream views of periodontal mechanical treatment. Therefore, this study is devoted to compare the clinical effect of ultrasonic subgingival debridement and ultrasonic subgingival scaling combined with manual root planing, which takes the implementation of root planing as the only variable and is more in line with the current clinical situation, thus hoping to provide some valuable reference to dentists. METHODS/DESIGN: Forty adult patients who fit the inclusion criteria are being recruited from the Peking University Hospital of Stomatology (Beijing, China). By means of randomization tables, one quadrant of the upper and lower teeth is the test group and the other is the control group. Test group: ultrasonic subgingival scaling combined with manual root planing. CONTROL GROUP: ultrasonic subgingival debridement. In a 24-week follow-up period, plaque index, probing depth, clinical attachment loss, bleeding index, furcation involvement, mobility, and patient-reported outcome (Visual Analog Scale for pain and sensitivity) will be observed and documented. DISCUSSION: This study evaluates the effectiveness of ultrasonic subgingival scaling combined with manual root planing and ultrasonic subgingival debridement alone in the nonsurgical treatment of periodontitis with a split-mouth design after 1, 3 and 6 months. The result of the trial should potentially contribute to an advanced treatment strategy for periodontitis with an ideal clinical outcome. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP), ID: ChiCTR1800017122. Registered on 12 July 2018.

Influence of CYP1A1 rs1048943 on Short- and Long-term Outcomes of Non-surgical Periodontal Therapy for Generalised Aggressive Periodontitis.

Objective: To investigate the influence of CYP1A1 rs1048943 on short- and long-term outcomes of nonsurgical periodontal therapy (NSPT) for generalised aggressive periodon- titis (GAgP). Methods: The CYP1A1 rs1048943 polymorphisms of 224 GAgP patients were genotyped by time-of-flight mass spectrometry. A total of 125 patients received NSPT and subsequent followup for 3 months. Of the 125 patients, 81 were followed for at least 3 years. Clinical periodontal parameters were collected at baseline and at the follow-up visits. Negative binomial regression was used to analyse the association between the number of teeth lost during the 3-year observation period and CYP1A1 rs1048943 genotypes. Results: The mean probing depth (PD) and percentage of sites with Bleeding Index (BI) ≥ 3 were all significantly greater in CYP1A1 rs1048943 G allele carriers than non-carriers at 3 months and 3 years after treatment (P < 0.05). In the PD ≥ 7 mm subgroup, the mean PD was significantly higher in G allele carriers than non-carriers at the 3-year follow-up (P < 0.05). The other clinical parameters did not show a similar trend (P > 0.05). Furthermore, the changes of percentage of sites with BI ≥ 3 were significantly smaller in G allele carriers than non-carriers at 3 months and 3 years after treatment (P < 0.05). GAgP patients with the GG genotype had lost more over the 3-year follow-up period compared with patients with the AA genotype (P < 0.05). Conclusion: These data indicated that the CYP1A1 rs1048943 AG/GG genotypes may influence the short- and long-term outcomes of NSPT in GAgP patients.

The association of EGF rs2237051 variant, serum EGF levels and generalized aggressive periodontitis: a preliminary study.

BACKGROUND: Epidermal growth factor (EGF) is a pro-inflammatory small peptide that stimulates cell growth, proliferation and differentiation through binding to its receptor. EGF rs2237051 and serum EGF levels have been demonstrated to be related with a variety of diseases, including several tumors and inflammatory diseases. Therefore, this study aims to investigate the association of the EGF rs2237051 variant and serum EGF levels in Chinese patients with generalized aggressive periodontitis (GAgP). MATERIAL AND METHODS: A case-control study was conducted among 216 patients with GAgP and 138 healthy controls. The clinical parameters of plaque index, probing depth, attachment loss and bleeding index were recorded. The EGF rs2237051 polymorphism was genotyped using time-of-flight mass spectrometry, and serum EGF levels were determined. Logistic and linear regression models were used to investigate the association between the genotypes of EGF rs2237051, serum EGF levels and GAgP risk. RESULTS: The AA genotype of EGF rs2237051 showed higher risk for GAgP than the combined genotypes GG and AG (adjusted OR = 1.65, 95% CI [1.06-2.57]). Increased serum EGF levels were associated with GAgP (adjusted OR = 1.18, 95% CI [1.14-1.22]). Moreover, the serum EGF level for the AA genotype was significantly higher than that for the AG/GG genotypes in patients with GAgP (adjusted ß = 4.70, 95% CI [2.09-7.31]). CONCLUSION: We demonstrated that EGF rs2237051 variant and the increased level of serum EGF were associated with the risk of GAgP, the serum EGF was up-regulated in patients with GAgP. It was indicated that serum EGF might be a biomarker of GAgP and EGF rs2237051 may be related to the genetic background of GAgP.

Periodontal Effect of Periodontally Accelerated Osteogenic Orthodontics in Skeletal Angle Class III: A Nonrandomized, Controlled Trial.

The objective of this study was to evaluate the effect of periodontally accelerated osteogenic orthodontics (PAOO) on gingivae and alveolar bone by analysis of clinical and cone beam computed tomography (CBCT) parameters in the treatment of 20 skeletal Class III patients. The patients included in this study were divided into test and control groups. Periodontal parameters such as probing depth (PD), gingival recession (GR), keratinized gingival width, and alveolar bone thickness of CBCT scans were measured and recorded preoperation (T0) and at 6 months postoperative (T1). The difference in PD from T0 to T1 between the two groups was not statistically significant (0.01 ± 0.46 mm vs 0.22 ± 0.65 mm, respectively; P > .05). No significant difference in GR was observed from T0 to T1 between the two groups (0.03 ± 0.26 mm vs -0.03 ± 0.27 mm, respectively; P > .05). Alveolar bone thickness (4 mm apical to the cementoenamel junction [CEJ]) change from T0 to T1 was -0.31 ± 0.35 mm for the control group and 0.06 ± 0.69 mm for the test group (P < .05). Meanwhile, alveolar bone thickness (6 mm apical to CEJ) changes from T0 to T1 were -0.38 ± 0.54 mm and 0.10 ± 0.80 mm for the control and test groups, respectively (P < .05). It was determined that PAOO in the treatment of skeletal Class III patients is effective and safe to periodontium on the basis of clinical and CBCT parameters.

A novel multi-locus genetic risk score identifies patients with higher risk of generalized aggressive periodontitis.

BACKGROUND: Each genetic variant individually explains only a tiny proportion of the genetic variation with insignificant predictive power. The tool of multi-locus genetic risk score (GRS), which aggregates information from multiple genetic variants, has been widely used in many complex diseases but not yet applied to generalized aggressive periodontitis (GAgP). METHODS: A total of 335 GAgP patients and 114 healthy controls were enrolled in the case-control study. The unweighted GRS (uGRS) and weighted GRS (wGRS) were calculated based on significant variants. Logistic regression models were conducted for the GRS-based association analyses on the risk of GAgP. Receiver operating characteristic analysis was performed to compare the discriminatory ability of predictors of GAgP risk. RESULTS: Four loci were found to be significantly associated with GAgP. They were matrix metalloproteinase 8 rs11225395 (odds ratio [OR] = 1.40, 95% CI: 1.03 to 1.91), epidermal growth factor rs2237051 (OR = 1.41, 95% CI: 1.03 to 1.93), PPAR-a rs4253623 (OR = 1.53, 95% CI: 1.03 to 2.26), and apolipoprotein E rs429358 (OR = 1.79, 95% CI: 1.08 to 2.97). Each additional point of the uGRS/wGRS was associated with a 50%/31% increased risk of developing GAgP (OR = 1.50, 95% CI: 1.21 to 1.85 or OR = 1.31, 95% CI: 1.14 to 1.51, respectively) after adjusting for age, sex, and body mass index (BMI). Participants in the high group of uGRS/wGRS (OR = 2.87, 95% CI: 1.59 to 5.17 or OR = 2.67, 95% CI: 1.46 to 4.88, respectively) and the middle group of uGRS/wGRS (OR = 2.21, 95% CI: 1.29 to 3.78 or OR = 1.88, 95% CI: 1.09 to 3.08, respectively) had an increased risk of GAgP compared with those in the low group of score after adjustment for age, sex, and BMI. The addition of GRS to a model of conventional risk factors improved discrimination by 4.5% (from 0.695 to 0.740, P = 0.048). CONCLUSIONS: We demonstrated that the multi-locus GRS based on four significant single nucleotide polymorphisms might be useful to assess genetic predisposition to GAgP. The GRS in combination with conventional risk factors significantly improved the power of identifying subgroups of Chinese population with a particularly high risk for GAgP.

Root abnormalities and nonsurgical management of generalized aggressive periodontitis.

To investigate long-term nonsurgical treatment outcomes in patients with generalized aggressive periodontitis (GAgP) and the impact of root abnormalities (RAs) and other patient-level factors in relation to GAgP progression. Patients (n = 64) from a GAgP cohort who completed active nonsurgical periodontal treatment and consented to re-evaluation after 3 to 11 (mean 5.3) years, were enrolled. RAs were identified using radiographs. Periodontal parameters (e.g., probing depths [PDs], and tooth loss [TL]) were investigated. Multivariate analysis was performed to identify factors contributing to TL and bone level alteration (∆BL). After treatment, the mean number of sites with PDs > 5 mm decreased from 54.3 to 17.2. Annual TL was 0.11/patient. Twenty-one patients (32.8%) had >4 teeth with root abnormalities (RA-teeth) and exhibited a higher risk for TL (univariate odds ration [OR] = 3.52, multivariate logistic OR = 6.57). Factors correlated to ∆BL were sites with residual PD > 5 mm (ß = -0.400) and observation time (ß = -0.210). Nonsurgical treatment provides beneficial outcomes in GAgP patients. Higher incidence of RAs and high prevalence of residual deep pockets have a negative impact on long-term outcomes. PRACTICAL IMPLICATIONS: in cases of GAgP with residual deep pockets and high incidence of RAs, clinicians must emphasize that long-term outcomes of nonsurgical treatment may be compromised.

Platelet activation and platelet-leukocyte interaction in generalized aggressive periodontitis.

Generalized aggressive periodontitis (GAgP) is an inflammatory disease of host response to bacterial challenge. To explore the role of platelets in host-microbial interactions in patients with periodontitis, 124 patients with GAgP and 57 healthy subjects were enrolled. Reliable indicators of subclinical platelet functional status, platelet count (PLT), platelet large cell ratio (PLCR), and mean platelet volume (MPV), were significantly lower in the GAgP group than in the control group and were negatively correlated with clinical periodontal parameters. The levels of important cytosolic protein in neutrophils, calprotectin (S100A8/A9) in plasma, and gingival crevicular fluid (GCF) were significantly higher in patients with GAgP compared with healthy subjects. Moreover, the GCF calprotectin level was negatively correlated with PLCR and MPV values. To explore the possible mechanisms of changes in platelet indices in periodontitis, flow cytometry analysis was performed, and patients with GAgP were found to have a higher status of platelet activation compared with healthy controls. Porphyromonas gingivalis (P. gingivalis) and recombinant human S100A8/A9 (rhS100A8/A9) induced platelet activation and facilitated platelet-leukocyte aggregate formation in whole blood of healthy subjects. In response to P. gingivalis and rhS100A8/A9, platelets from patients with GAgP increased activation and increased formation of platelet-leukocyte aggregates compared with those from healthy subjects. Platelet aggregates and platelets attached to leukocytes were found on gingival tissues from patients with GAgP, suggesting that decreased platelet size and count in the circulation might be related to consumption of large, activated platelets at inflamed gingiva. Platelets may have a previously unrecognized role in host response to periodontal infection.

GC Gene Polymorphisms and Vitamin D-Binding Protein Levels Are Related to the Risk of Generalized Aggressive Periodontitis.

Objective. To explore whether GC (group-specific component) rs17467825, rs4588, and rs7041 polymorphisms are associated with generalized aggressive periodontitis. Methods. This case-control study recruited 372 patients with generalized aggressive periodontitis (group AgP) and 133 periodontal healthy subjects (group HP). GC rs17467825, rs4588, and rs7041 genotypes and plasmatic vitamin D-binding protein (DBP) were measured. Analysis of single SNP and multiple SNPs was performed and relevance between plasmatic DBP and haplotypes was analyzed. Results. GC rs17467825 GG genotype was statistically associated with lower risk for generalized aggressive periodontitis under the recessive model (OR = 0.52, 95% CI: 0.30-0.92, p = 0.028). GC rs17467825 and rs4588 had strong linkage disequilibrium with r2 ≥ 0.8 and D' ≥ 0.8. Haplotype (GC rs17467825, rs4588) GC was associated with the less risk for generalized aggressive periodontitis (OR = 0.29, 95% CI: 0.09-0.96, p = 0.043). In group AgP, individuals with combined genotype (GC rs17467825, rs4588) AG+CA had significantly lower plasmatic DBP level than those with the other two combined genotypes (AG+CA versus AA+CC p = 0.007; AG+CA versus GG+AA p = 0.026). Conclusions. GC rs17467825 genotype GG and haplotype (GC rs17467825, rs4588) GC are associated with generalized aggressive periodontitis. The association may be acquired through regulating DBP levels. The functions of GC gene and DBP in inflammatory disease need to be further studied.

The Effects of Initial Periodontal Therapy on the Serum Receptor Activator of Nuclear Factor-κß Ligand/Osteoprotegerin System in Patients With Type 2 Diabetes Mellitus and Periodontitis.

BACKGROUND: The aim of the present study is to evaluate the serum receptor activator of nuclear factor-κß ligand (RANKL)/osteoprotegerin (OPG) system in patients with chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM) and its changes after periodontal intervention. METHODS: Thirty-five patients with CP + T2DM, 35 systemically healthy patients with CP, and 35 healthy controls were enrolled, and serum levels of RANKL and OPG were measured at baseline. Then the CP + T2DM group was divided into a well-controlled subgroup and a poorly controlled subgroup according to their hemoglobin A1c (HbA1c), and initial periodontal therapy was performed. After 3 months, patients in both subgroups were recalled, and serum RANKL and OPG levels were tested again and compared with the baseline. RESULTS: At baseline, serum levels of OPG in the T2DM + CP group were much lower than in the CP group and healthy controls (197.41 ± 57.05 pg/mL versus 232.60 ± 70.85 pg/mL [CP group] or 244.96 ± 85.13 pg/mL [healthy controls], P <0.05), whereas their RANKL levels were much higher than in the other two groups (324.35 ± 87.62 pg/mL versus 284.52 ± 90.35 pg/mL [CP group] or 163.01 ± 45.24 pg/mL [healthy control], P <0.05), as was the RANKL/OPG (R/O) ratio (1.68 ± 0.33 versus 1.26 ± 0.35 [CP group] or 0.72 ± 0.25 [healthy control], P <0.001). Serum levels of OPG in both disease groups had significant negative correlations with HbA1C, and serum levels of RANKL in all participants had significant positive correlations with periodontal parameters. After periodontal intervention, both the well-controlled and poorly controlled subgroups exhibited significant increases in OPG and decreases in RANKL in serum, and the R/O ratio was also notably reduced. Additionally, the poorly controlled subgroup exhibited a greater reduction in HbA1c and a greater increase in OPG than the well-controlled subgroup. CONCLUSIONS: The changing trend in the serum RANKL/OPG system in patients with T2DM + CP was similar to that seen in CP patients and may be even more pronounced. Periodontal intervention effectively improved glucose metabolism and changed the serum RANKL/OPG system regardless of whether patients' HbA1c was well-controlled or poorly controlled over the 3-month observation period.