Periodontitis and hypertension are linked through systemic inflammation: A 5-year longitudinal study.

AIM: To investigate the associations between periodontitis and hypertension and potential mediation via systemic inflammation through a 5-year longitudinal study. MATERIALS AND METHODS: The severity and extent of periodontitis were determined using probing depth (PD). Oral hygiene was assessed using plaque scores. The associations between periodontal variables and 5-year blood pressure changes or incident hypertension were analysed using linear or Poisson regression, adjusting for potential confounders. Mediation analysis of two systemic inflammatory biomarkers, namely white blood cell count (WBC) and C-reactive protein (CRP) levels, was performed. RESULTS: The study population included 901 hypertension-free participants, aged 50-73 years. Greater mean PD, higher percentage of sites with PD ≥ 6 mm and poor oral hygiene were associated with elevated systolic blood pressure and increased hypertension risk (relative risks = 1.17 [95% confidence interval [CI]: 1.02-1.34], 1.13 [95% CI: 1.02-1.26] and 1.08 [95% CI: 1.03-1.13], respectively). Periodontitis and poor oral hygiene were associated with higher WBC and CRP levels (p < .05), which, in turn, were associated with increased hypertension risk (p < .05). WBC and CRP jointly mediated 14.1%-26.9% of the associations between periodontal variables and incident hypertension. CONCLUSIONS: Periodontitis and poor oral hygiene were associated with increased hypertension risk, and systemic inflammation was, in part, a mediator of these associations.

Interplay between vitamin D receptor FokI polymorphism and smoking influences Porphyromonas gingivalis proportions in subgingival plaque.

AIM: This cross-sectional study investigated the effect of the vitamin D receptor (VDR) FokI polymorphism and its interactions with smoking/drinking on the proportions of periodontal pathogens and periodontitis severity. MATERIALS AND METHODS: FokI genotyping and bacterial quantification were performed using real-time polymerase chain reaction. Periodontitis severity was determined using mean clinical attachment level (CAL). Regression analyses examined the associations between the FokI polymorphism (rs2228570) and bacterial proportions or periodontitis severity. Effect modification by smoking or drinking was assessed. RESULTS: The study population comprised 1,460 individuals, aged 39-66 years. After multivariable adjustment, the FokI risk genotypes (CC + CT) were associated with elevated Porphyromonas gingivalis proportions (regression coefficient (ß) =0.294 ± 0.139; p = .034) and increased mean CAL (ß = 0.130 ± 0.048; p = .007). The effect of the FokI polymorphism on P. gingivalis proportions was greater in smokers (ß = 0.897 ± 0.328; p = .006) compared to non-smokers (ß = 0.164 ± 0.153; p = .282) and in drinkers (ß = 0.668 ± 0.242; p = .006) compared to non-drinkers (ß = 0.114 ± 0.169; p = .500). The genotype*smoking interaction for P. gingivalis proportions was significant (p = .043), whereas the genotype*drinking interaction was not (p = .061). Similar results were found for the effect of the genotype*smoking/drinking interaction on mean CAL. CONCLUSIONS: These findings suggest that the interplay between the host genotype and smoking is important in determining the subgingival microbial composition and periodontitis severity.

Periodontitis is associated with elevated serum levels of cardiac biomarkers-Soluble ST2 and C-reactive protein.

AIM: This cross-sectional study examined the associations between periodontitis and the serum cardiac biomarkers-soluble ST2 (sST2) and C-reactive protein (CRP)-in systemically healthy adults. MATERIALS AND METHODS: Periodontitis severity was determined using mean probing depth (PD) or clinical attachment level (CAL) and a categorical variable (no/mild, moderate, or severe). Oral hygiene was evaluated using plaque scores. Regression analyses assessed the associations between periodontal variables and sST2 or CRP levels, adjusting for age, sex, smoking, body mass index, systolic blood pressure, fasting plasma glucose, and high-density or low-density lipoprotein cholesterol. RESULTS: The study population comprised 799 individuals, aged 50-73 years. After multivariable adjustment, greater mean PD/CAL, severe periodontitis, and poor oral hygiene were associated with elevated sST2 and CRP levels (p < 0.05). Greater mean PD or CAL was associated with increased odds of having sST2 in the top quintile (>22.7 µg/L) (odds ratio [OR] [95% confidence interval (CI)]: 1.7 [1.1-2.4] and 1.3 [1.1-1.7], respectively) and CRP > 3 mg/L (OR: 1.5 [1.1-2.1] and 1.3 [1.0-1.5], respectively). Individuals with poor oral hygiene were more likely to have sST2 > 22.7 µg/L (OR: 2.0 [1.0-4.0]) and CRP > 3 mg/L (OR: 2.0 [1.1-3.5]), compared to those with good oral hygiene. CONCLUSIONS: Periodontitis and poor oral hygiene were associated with elevated serum sST2 and CRP levels.

Mediation analysis of systemic inflammation on the association between periodontitis and glycaemic status.

AIM: This cross-sectional study investigated the associations between periodontitis, systemic inflammation and glycaemic status. MATERIALS AND METHODS: The participants were divided into three groups: normoglycaemia, impaired fasting glucose (IFG) and diabetes. Multinomial logistic regression was used to examine the associations between periodontitis severity and glycaemic status, adjusting for potential confounders. Mediation analysis of four systemic inflammatory biomarkers, C-reactive protein (CRP), white blood cell count (WBC), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), was performed. RESULTS: This study comprised 2,036 participants, aged 39-66 years. Severe periodontitis was associated with IFG and diabetes with odds ratios of 1.6 (95% confidence interval [CI]: 1.1-2.4, p = .023) and 2.4 (95% CI: 1.3-4.5, p = .006), respectively. The CRP, WBC and PLR were associated with both periodontitis severity and glycaemic status (p < .05). In contrast, the NLR was associated with periodontitis severity (p < .05) but not glycaemic status (p > .05). The CRP, WBC and PLR mediated 8%, 13% and 6%, respectively, of the association between severe periodontitis and diabetes. Similar proportions mediated were observed for the periodontitis-IFG association. CONCLUSIONS: Our findings support the role of systemic inflammation as mediators of the associations between periodontitis and IFG or diabetes.

Vitamin D Receptor Gene Polymorphism and Smoking in the Risk of Chronic Periodontitis.

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in susceptibility to infections and bone-related diseases. However, their relationship with periodontal disease remains unclear. This cross-sectional study investigates whether susceptibility to chronic periodontitis (CP) in a Thai population is associated with VDR polymorphisms. METHODS: Genomic DNA was obtained from 1,460 participants, aged 39 to 66 years. Genotyping of VDR polymorphisms (FokI, BsmI, ApaI, and TaqI) was performed using real-time polymerase chain reaction. Participants were categorized into three groups: 1) no/mild; 2) moderate; and 3) severe CP. Multinomial logistic regression was used to determine degree of association between VDR polymorphisms and periodontal status adjusted for known confounders. RESULTS: The CC+CT genotypes of FokI polymorphism were associated with severe CP with an odds ratio (OR) of 1.9 (95% confidence interval [CI]: 1.3 to 2.8). Compared with genotype-negative (TT) non-smokers, positivity for the risk genotypes (CC+CT) alone and current smoking alone were associated with severe CP with ORs of 1.8 (95% CI: 1.1 to 3.2) and 2.5 (95% CI: 1.0 to 6.2), respectively. The combination of being genotype positive and smoking further increased the OR to 9.6 (95% CI: 4.5 to 20.4). This combined effect was 3.7 times (95% CI: 1.2 to 11.1) greater than expected from the sum of their individual effects, indicating a synergistic interaction. No significant association was observed between other polymorphisms and CP. CONCLUSION: FokI CC+CT genotypes were associated with increased susceptibility to severe CP, which was aggravated further when combined with smoking.

Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population.

Periodontitis is a polymicrobial infection of tooth-supporting tissues. This cross-sectional study aimed to examine the associations between five target species and severe periodontitis in a Thai population. Using the CDC/AAP case definition, individuals diagnosed with no/mild and severe periodontitis were included. Quantitative analyses of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi) in subgingival plaque were performed using real-time polymerase chain reaction. The association between target species and severe periodontitis was examined using logistic regression analysis. The study subjects comprised 479 individuals with no/mild periodontitis and 883 with severe periodontitis. Bacterial prevalence and quantity were higher in subjects with severe periodontitis than in those with no/mild disease. In the fully adjusted model, all species except Tf showed a dose-dependent relationship with periodontitis. The mere presence of Pg, even in low amount, was significantly associated with severe periodontitis, while the amount of Aa, Td, and Pi had to reach the critical thresholds to be significantly associated with disease. Compared to individuals with low levels of both Td and Pi, high colonization by either Td or Pi alone significantly increased the odds of having severe periodontitis by 2.5 (95%CI 1.7-3.5) folds. The odds ratio was further increased to 14.8 (95%CI 9.2-23.8) in individuals who were highly colonized by both species. Moreover, the presence of Pg and high colonization by Aa were independently associated with severe periodontitis with odds ratios of 5.6 (95%CI 3.4-9.1) and 2.2 (95%CI 1.5-3.3), respectively. Our findings suggest that the presence of Pg and high colonization by Aa, Td, and Pi play an important role in severe periodontitis in this study population. We also demonstrate for the first time that individuals co-infected with Td and Pi were more likely to have periodontitis than were those infected with a single pathogen.

Cytotoxicity of flowable resin composite on cultured human periodontal ligament cells compared with mineral trioxide aggregate.

AIM: To investigate the cytotoxicity of three flowable resin composites that potentially useful as retrograde filling materials, compared with mineral trioxide aggregate (MTA). METHODS: Ten standard cylinder discs were used for each of the tested materials: Tetric Flow, Filtex Flow, Aeliteflo, and MTA, which were prepared under aseptic conditions. Cytotoxicity of eluates from all materials after 1-4 days' immersion in culture medium and direct contact cytotoxicity were evaluated using cultured human periodontal ligament cells (PDLC). The colorimetric (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and scanning electron microscope of cell morphology (direct contact only) were used. RESULTS: No eluates of set materials demonstrated cytotoxicity at any concentration or elution time. Freshly-mixed MTA was cytotoxic in direct contact, but not set MTA. Freshly-mixed Aeliteflo was also cytotoxic, as was set material up to 2 days' elution. With morphological assessment, some differences were seen among resin composites, but all changes were rated as slight using the International Standard Organization criteria. CONCLUSIONS: Of all of the materials tested, Tetric Flow showed the least cytotoxic effects on PDLC. Further research is needed to determine the clinical usefulness of flowable composites as retrograde filling materials.

Aggregatibacter actinomycetemcomitans serotypes, the JP2 clone and cytolethal distending toxin genes in a Thai population.

AIM: To examine the genetic diversity of Aggregatibacter actinomycetemcomitans in Thai adults. MATERIALS AND METHODS: Subgingival plaque samples from 453 subjects were analysed for A. actinomycetemcomitans serotypes, the presence of the high leukotoxin-producing JP2 clone and cytolethal distending toxin genes (cdtABC) using the polymerase chain reaction technique. In subjects who were positive for cdtABC, restriction fragment length polymorphism analysis was used to identify a single nucleotide polymorphism (SNP) in the cdtB gene at amino acid position 281. The extent and severity of periodontal disease were compared between subjects harbouring different A. actinomycetemcomitans genotypes. RESULTS: Eighty six subjects (19%) were positive for A. actinomycetemcomitans. The JP2 clone was not detected. Serotype c was the most prevalent (57%), followed by serotypes a (33%) and b (7%). Among A. actinomycetemcomitans-positive subjects, 27% were positive for cdtABC. All cdtABC-positive subjects possessed the SNP in the cdtB, which is involved with increased toxin activity. The presence of A. actinomycetemcomitans, but not a specific genotype, was significantly related to increased probing depth and periodontal attachment loss. CONCLUSIONS: Our results confirm the previous findings that genotype distribution of A. actinomycetemcomitans varies between ethnic groups. However, no clear relationship between a specific genotype and periodontal conditions was observed.

Association between cigarette smoking and the intraoral distribution of periodontal disease in Thai men over 50 years of age.

AIM: This study aimed to investigate the effects of cigarette smoking on periodontal conditions in specific tooth regions of older Thai men. METHODS: There were 272 current smokers, 714 former smokers, and 477 non-smokers enrolled in the present study. Differences between groups in the mean probing depth or attachment loss were compared using ancova. The relationship between smoking exposure or cessation duration and periodontal conditions was examined using linear trend analysis. RESULTS: Smokers had deeper pockets and attachment loss than non-smokers. The greatest differences between smokers and non-smokers were observed in the maxillary posterior palatal region, where current smokers had 0.88 mm greater attachment loss than non-smokers, compared to 0.36-0.60 mm observed in other tooth regions. Among the current smokers, there was a trend towards an increase in attachment loss with increasing smoking exposure in the maxillary posterior regions. However, it was not statistically significant. Among the former smokers, a better periodontal condition was observed, depending on the length of time since smoking cessation; this was most pronounced in the maxillary posterior palatal region. CONCLUSIONS: The palatal site of maxillary posterior teeth was the area most affected by cigarette smoke. The results suggest a possible local effect of smoking in addition to its systemic effects.

Relationship between the presence of certain bacterial pathogens and periodontal status of urban Thai adults.

BACKGROUND: The association between Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T. forsythensis) and periodontal disease has been reported in Western populations. However, corresponding data in Asian populations are still lacking. The aim of this study was to determine the prevalence of these three bacteria and their relationship to periodontal status in a group of urban Thai adults. METHODS: The study was conducted in 453 subjects, aged 39 to 59 years. The presence of bacteria in subgingival plaque was analyzed using polymerase chain reaction analysis. Subjects were classified as having chronic periodontitis if they had at least three sites with probing depths > or =5 mm. Logistic regression analysis was used to determine the degree of association between the target bacteria and periodontal status. RESULTS: A. actinomycetemcomitans, P. gingivalis, and T. forsythia were found in 19.0%, 70.9%, and 77.5% of the subjects, respectively. About one-third (36.2%) of subjects had chronic periodontitis. In univariate analysis, age, male gender, current smoking, diabetes, and the presence of A. actinomycetemcomitans or P. gingivalis were positively associated with chronic periodontitis, whereas education and income exhibited inverse associations with chronic periodontitis. In multivariate analysis, education, current smoking, diabetes, and the presence of A. actinomycetemcomitans and P. gingivalis remained significant. The adjusted odds ratios for having chronic periodontitis were 2.5 and 3.4 in subjects positive for A. actinomycetemcomitans and P. gingivalis, respectively. However, no significant association was observed between the presence of T. forsythia and periodontal status. CONCLUSION: The presence of A. actinomycetemcomitans and P. gingivalis, but not T. forsythia, in subgingival plaque was associated with chronic periodontitis in this group of Thai adults.

Langerhans' cell histiocytosis in a 5-year-old girl: evidence of periodontal pathogens.

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disorder characterized by Langerhans' cell proliferation in various organs or tissues. When periodontal tissue is involved, clinical manifestations can vary from gingival recession and pocket formation to severe alveolar bone loss. This case report describes periodontal pathogens found in the pockets of involved primary teeth. METHODS: A 5-year-old girl with LCH presented with loose teeth. Intraoral examination and radiographs revealed deep pockets and severe bone loss around all primary molars. Bacterial samples were obtained from saliva and subgingival plaque and analyzed for the presence of five periodontopathic bacteria using a polymerase chain reaction (PCR) method. Due to severe periodontal destruction, all primary molars were extracted, and a gingival biopsy was taken from tooth T to confirm the diagnosis of LCH. RESULTS: The biopsy specimen revealed the histologic features of LCH. The patient was diagnosed as having periodontitis as a manifestation of LCH. PCR results of subgingival plaque from LCH-affected molars indicated the presence of Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, and Prevotella intermedia. However, Actinobacillus actinomycetemcomitans was absent from these teeth. No tested bacteria were found in the non-affected anterior teeth. CONCLUSIONS: The bacteria commonly associated with periodontal disease were detected in subgingival plaque samples from this LCH patient. More microbiological data are required to understand the role of these bacteria in LCH-associated periodontal destruction.

Risk indicators of periodontal disease in older Thai adults.

BACKGROUND: The aim of this study was to identify risk indicators for periodontitis using cross-sectional data from a group of older Thai adults. METHODS: The study group consisted of 2,005 individuals, aged 50 to 73 years old. They received detailed medical examinations and periodontal examinations including plaque score, probing depth, and clinical attachment level. These individuals were categorized into mild, moderate, or severe periodontitis if mean clinical attachment level was <2.5 mm, 2.5 to 3.9 mm, or > or = 4.0 mm, respectively. The degree of association between the severity of periodontitis and various independent variables was investigated using multinomial logistic regression analysis. RESULTS: The percentage of subjects classified as mild, moderate, and severe periodontitis was 30.5, 53.6, and 15.9, respectively. The prevalence of severe periodontitis was higher in males and increased with age. In univariate analysis, older subjects, males, less educated persons, persons with lower income, persons with higher plaque score, smokers, drinkers, and diabetics were more likely to have both moderate and severe periodontitis. In multivariate analysis, males, less educated persons, persons with higher plaque score, and current smokers were more likely to have moderate periodontitis. Three additional factors including older age, former smokers, and diabetes significantly increased the odds for having severe periodontitis. Income, alcohol consumption, body mass index, and waist circumference had no significant effects on periodontal disease severity in the multivariate model. CONCLUSIONS: Our data suggest that age, gender, education, oral hygiene status, smoking, and diabetes are significantly associated with periodontal disease severity in this study group. Longitudinal studies will establish whether these variables are true risk factors.

The effect of cigarette smoking on the severity of periodontal disease among older Thai adults.

BACKGROUND: The aim of this study is to determine the effect of cigarette smoking on the severity of periodontitis in a cross-sectional study of older Thai adults. METHODS: The study population consisted of 1,960 subjects (age 50 to 73 years old). All subjects received both medical and dental examinations. Periodontal examinations, including plaque score, probing depth, and clinical attachment level, were done on all teeth present in two diagonal quadrants. Sociodemographic characteristics and smoking status were obtained by questionnaires. Multinomial logistic regression was used to address the association between cigarette consumption and mean clinical attachment level. RESULTS: In this study population, 48.7% were non-smokers, 14.4% were current smokers, and 36.9% were former smokers. Current smokers had higher percentage of sites with plaque, deeper mean probing depth, and greater mean clinical attachment level than former smokers and non-smokers. The odds of having moderate and severe periodontitis for current smokers were 1.7 and 4.8 times greater than non-smokers, respectively. Former smokers were 1.8 times more likely than non-smokers to have severe periodontitis. Quitting smoking reduced the odds of having periodontitis. For light smokers (<15 packyear), the odds for severe periodontitis reverted to the level of non-smokers when they had quit smoking for > or =10 years. For moderate and heavy smokers (> or =15 packyear), the odds of having severe periodontitis did not differ from those of non-smokers when they had quit smoking for > or =20 years. CONCLUSIONS: There was a strong association between cigarette smoking and the risk of periodontitis among older Thai adults. Quitting smoking appears to be beneficial to periodontal health.

Nmp4/CIZ regulation of matrix metalloproteinase 13 (MMP-13) response to parathyroid hormone in osteoblasts.

Parathyroid hormone (PTH) regulation of matrix metalloproteinase-13 (MMP-13) expression in osteoblasts contributes to normal bone turnover. The PTH response region of the rat MMP-13 gene spans nucleotides (nt) -148 to -38 and supports binding of numerous transcription factors, including Runx2, necessary for osteoblast differentiation, c-Fos/c-Jun, and Ets-1. These trans-acting proteins mediate hormone induction via incompletely defined combinatorial interactions. Within this region, adjacent to the distal Runx2 site, is a homopolymeric(dA:dT) element (-119/-110 nt) that conforms to the consensus site for the novel transcription factor nuclear matrix protein-4/cas interacting zinc finger protein (Nmp4/CIZ). This protein regulates bone cell expression of type I collagen and suppresses BMP2-enhanced osteoblast differentiation. The aim of this study was to determine whether Nmp4/CIZ contributes to MMP-13 basal transcription and PTH responsiveness in osteoblasts. Electrophoretic mobility shift analysis confirms Nmp4/CIZ binding within the MMP-13 PTH response region. Mutation of the Nmp4/CIZ element decreases basal activity of an MMP-13 promoter-reporter construct containing the first 1329 nt of the 5'-regulatory region, and overexpression of Nmp4/CIZ protein enhances the activity of the wild-type promoter. The same mutation of the homopolymeric(dA:dT) element enhances the MMP-13 response to PTH and PGE(2). Overexpression of Nmp4/CIZ diminishes hormone induction. Mutation of both the homopolymeric(dA:dT) element and the adjacent Runx2 site further augments the PTH response. On the basis of these data and previous studies, we propose that Nmp4/CIZ is a component of a multiprotein assemblage or enhanceosome within the MMP-13 PTH response region and that, within this context, Nmp4/CIZ promotes both basal expression and hormonal synergy.

DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors.

Splice variants of the Nmp4 gene include nuclear matrix transcription factors that regulate the type I collagen alpha1(I) polypeptide chain (COL1A1) promoter and several matrix metalloproteinase (MMP) genes. To date, these are the only Cys(2)His(2) zinc finger proteins known to bind within the minor groove of homopolymeric (dA.dT) DNA. Nmp4 isoforms contain from 5 to 8 Cys(2)His(2) zinc fingers, an SH3-binding domain that overlaps with a putative AT-hook and a polyglutamine-alanine repeat (poly(QA)). To determine the mechanistic significance of Cys(2)His(2) zinc finger association with this unusual consensus DNA binding element, we identified the Nmp4 DNA-binding and transcriptional activation domains. Zinc fingers 2, 3, and 6 mediated association with the homopolymeric (dA.dT) COL1A1/MMP DNA consensus element. The N terminus of the Nmp4 protein exhibited a strong trans-activation capacity when fused to the GAL4 DNA-binding domain, but this activity was masked within the context of the full-length Nmp4-GAL4 DNA-binding domain chimera. However, upon binding to the COL1A1/MMP homopolymeric (dA.dT) element, the native Nmp4 protein up-regulated transcription, and the poly(QA) domain acquired a significant role in trans-activation. We propose that allosteric effects induced upon zinc finger association with the homopolymeric (dA.dT) minor groove confer context-specific functionality to this unusual family of Cys(2)His(2) transcription factors.