Evidence of a substantial genetic basis for IgG2 levels in families with aggressive periodontitis

IgG2 is elevated in localized but not in generalized aggressive periodontitis (AgP). Exposure to pathogenic bacteria is essential for disease. Immune responses are dominated by IgG2 reactive with bacterial surface carbohydrates. We used variance component analyses to assess IgG2 heritability and determine whether genes that influence IgG2 are the same genes that influence disease susceptibility. We studied 17 Caucasian and 43 African American families with two or more localized or generalized AgP-affected members (274 subjects with IgG2 measurements). Only 16% of the variance in IgG2 was attributable to age, race, and smoking. Even with the addition of localized AgP, the model still explained only 19% of IgG2 variance. By contrast, heritability of IgG2 levels was estimated to be 38% and highly significant (P = 0.0006), demonstrating a substantial genetic basis. Bi-trait variance component analyses of IgG2 and quantitative measures of AgP indicate that different genes appear to control IgG2 levels and disease susceptibility.     

Molecular genetic detection of Bacteroides heparinolyticus in adult periodontitis

Bacteroides heparinolyticus in subgingival plaque was identified using a digoxigen-in-labeled whole genomic DNA probe and a polymerase chain reaction (PCR) assay based on 16S rRNA species-specific primers (5'-ATG GTG ATT CCG CAT GGT TTC TCC-3'(base position, 188-212) and 5'-CAA ACT TTC ACA GCT GAC TTA AGC-3'(592-615)). Subgingival specimens obtained by paper points from 3 deep periodontal pockets in each of 113 adults were examined. The DNA probe reacted with all pure isolates tested of B. heparinolyticus and did not react with other oral species tested; the probe showed positive reactions in 74.3% of the patient samples examined. The PCR primers produced the 428 bp species specific amplification product in all B. heparinolyticus test strains and did not reveal detectable amplicons with strains of other subgingival species. The PCR method detected 50 B. heparinolyticus cells dispersed in subgingival plaque. PCR only revealed B. heparinolyticus in 6.2% of the patient samples studied. The higher level of positive specimens with the DNA probe was probably due to false-positive reactions from cross-hybridization with unknown subgingival species. This study suggests that the PCR method amplifying specific 16S rRNA sequences represents an easy and valuable means to detect B. heparinolyticus in subgingival plaque. The low prevalence of subgingival B. heparinolyticus does not incriminate the organism in the etiology of adult periodontitis.     

Evidence and a novel hypothesis for the role of dendritic cells and Porphyromonas gingivalis in adult periodontitis

We have proposed a novel overall hypothesis and approach to understanding the pathophysiology of adult periodontitis, one of the most common diseases that afflicts the US population. While mortality of the dentition is the most familiar outcome of adult periodontitis, its links with other more severe diseases, including coronary artery disease, respiratory diseases and pre-term labor, cannot be ignored We have called attention to the many intriguing parallels between adult periodontitis and contact hypersensitivity (GHS). CHS is among the most commor of dermatoses that afflicts mankind and one of the most intensively studied of in vivo immune responses. Both adult periodontitis and CHS target the host integument (gingiva or skin) and appear to involve the activation and sensitization of similar subsets of antigen capture and presenting cells, the dendritic cells (DCs), as well as similar T cell subsets. DCs have been termed “nature's adjuvant”, being more efficient at antigen-presentation than macrophages or B cells and the only antigen-presenting cells that can stimulate naive T cells to proliferate. This immunostimulatory capacity can also have detrimental effects for the host, as typified by graft-vs.-host disease and CHS responses. Both AP and CHS involve a predominantly destructive T cell response mediated by both regulatory and effector T cells. In the present paper, we show intriguing evidence that Porphyromonas gingivalis is a unique pathogen in this regard, able to infect, sensitize and activate DCs in vitro and, probably, in situ. Many questions about the role of P. gingivalis-sensitized DCs in adult periodontitis, and of the parallels between adult periodontitis and CHS, however, remain to be answered.     

Evidence for periodontitis as a tertiary vascular infection

Periodontal infections create an oral wound that serves as a portal for the systemic dissemination of oral pathogens. Clinical assessments of periodontal disease that account for the number and severity of diseased periodontal sites and teeth; including measurements of pocketing, the degree of redness, inflammation and bleeding on probing, can all provide an estimate of the severity of the clinical condition. However, these clinical signs appear inadequate to completely characterize the size, patency and integrity of the periodontal lesion which serves as a portal for systemic exposure. Increasingly, measures of infectious exposure including systemic antibodies, inflammatory mediators and acute phase reactants serve as surrogates or biomarkers for periodontal disease that provide further insight into the linkages between periodontitis and atherogenesis. This review discusses the evidence for systemic inflammatory responses to oral organisms and the potential role of chronic vessel pathology as a manifestation of tertiary periodontal infections.     

Smoking as a risk factor for periodontitis

Smokers have a higher susceptibility for periodontitis than non-smokers. Smoking is associated with more loss of attachment, progressive periodontal breakdown and also with a poor response to periodontal treatment. This is caused by the direct effect of nicotine on several factors that play a bacterial attack. These factors include the gingival vascularization and cellular defense mechanisms. The periodontal status of former smokers is intermediate to that of those who have never smoked and current smokers. Smoking cessation seems to have a beneficial effect on periodontal health.     

Not all patients are the same: systemic risk factors for adult periodontitis

Periodontal diseases are viewed today as multifactoral problems that are initiated and sustained by bacteria but significantly modified by the body's response to bacterial plaque. Local and systemic risk factors are involved in the disease process and both should be included when prognosis and treatment plans are developed. The most significant systemic modifying factors appear to be smoking, diabetes, and a recently discovered genetic marker. Slight changes in genes that produce an important inflammatory mediator, found in one-third of those studied, can lead to major negative outcomes in the way the body responds to bacteria.     

Evidence of a contribution of genetic factors to dental caries risk

Dental practitioners would find value in understanding the genetic contribution to caries risk for at least 2 reasons. First, they would be able to explain to patients that some forms of decay are more strongly associated with inherited risk. This would help explain for both the patient and dentist why persons with similar behavioral risks (eg, tooth brushing frequency or dietary habits) have different caries rates, thus avoiding the “blaming the victim” that sometimes accompanies preventive health messages in dentistry. In addition, future technological developments may make it possible to some day identify patients who are genetically at higher risk for caries. These patients then could be monitored more closely and provided with more aggressive prevention programs.

SUBJECTS

The literature was searched for evidence of a contribution of genetic factors to increased or decreased risk for dental caries. A search for global evidence of caries heritability was carried out using twin studies. Next, separate searches were carried out for evidence of heritability for 3 potential mechanisms associated with caries risk that included variation in the quality of the dental hard tissues, variation in host immune response, and variation in sugar metabolism. Each of the 4 searches is treated separately below. Inclusion criteria for the selected studies were not provided. No meta-analysis was attempted, since the selected studies, particularly twin studies, employed different statistical models to assess heritability (correlation coefficients, concordance rates, heritability estimates and intra-pair twin co-variation).

1. Twin Studies of Global Evidence of Dental Caries Heritability

- 10 articles employing the twin model study design (a total of 609 pairs of monozygotic (MZ) twins and 569 pairs of dizygotic (DZ) twins)

- 50% of studies with children and adolescents of an age range of 3 to 17 years

- 40% of studies in young adults and adults

2. Studies of Inherited Variations in Dental Enamel

- 4 reports employing cohort and case-control study designs in participants with epidermolysis bullosa

3. Studies of Inherited Variations in Immune Response

- 7 reports of MHC analysis (immune complex genes) utilizing cohort and case-control study designs

- At least 60% of the studies were in adults

4. Studies of Inherited Variations in Dietary Patterns and Sugar Metabolism

- Literature too scarce to permit evidence-based review

-. EXPOSURE

Genetic factors that lead to variations in hard tissue quality, immune response, and sugar metabolism.

MAIN OUTCOME MEASURE

1. The primary outcome measure was dental caries phenotypic expression measured as Delayed, Missing, Filled (DMF) or def.

2. Secondary outcome measures included enamel content and cariogenic bacteria (the mutans streptococci and lactobacilli).

MAIN RESULTS

1. Twin studies provided evidence that a genetic contribution to dental caries phenotypic variation exists (Table 1).

2. The epidermolysis bullosa syndrome provides evidence for a gene defect directly altering the tooth structure and rendering it more susceptible to dental caries.

3. Genes in the Human Leucocyte Antigen complex are associated with altered enamel development, increased risk for dental caries and increased predisposition to cariogenic infections.

4. Evidence-based review did not reveal or made it possible to identify any links between inherited alterations in sugar consumption.

     

Association between genetic risk score and periodontitis onset and progression: a pilot study

Aim

Recent research has focused attention on the single nucleotide polymorphisms (SNPs) involved in the host response in periodontitis. However, so as to combine the relatively small effects of individual genes the use of multi locus genetic risk (GRS) has been proposed. This study aims to evaluate whether the genetic risk score may predict periodontitis onset and progression.

Materials and methods

Fifty patients were divided into various groups according to periodontal status. Total DNA was isolated from epithelial oral cells by a masked operator and the selected SNPs were analysed. A GRS was calculated using an additive model.

Results

We found a strong association only between TNF rs1800629 and diffused forms of periodontitis. Data show that GRS is able to discriminate diffused forms of periodontitis from localized ones. Finally, a progressive increase of the GRS is evident in advanced periodontitis in comparison with early forms.

Discussion

In recent years, research on genetic polymorphism has had limited success in predicting the susceptibility to periodontal disease. However, our results indicate that the use of the genetic risk score could be promising. Further studies are necessary to include data from multiple genes so as to confirm our result.     

Evidence for a specific crevicular lymphocyte profile in aggressive periodontitis

BACKGROUND AND OBJECTIVE: It is undisputed that the periodontal pocket is a particular region of the host defense that is dominated by polymorphonuclear leukocytes. However, little is known about the lymphocytes in the crevice. It was the aim of this study to analyse the proportions of T cells (CD3+), T-helper cells (CD4+), T-suppressor cells (CD8+), and B cells (CD20+) in the crevice of patients with localized aggressive periodontitis (LAP), generalized aggressive periodontitis (GAP), and generalized chronic periodontitis (CP). The results were compared with those obtained from periodontally healthy controls. MATERIAL AND METHODS: Crevicular cells were collected according to a previously described method. The lymphocyte subpopulations were analysed by using an indirect immunofluorescence method. RESULTS: Significant differences were established between the test groups and the controls regarding the mean number of CD8+ lymphocytes (LAP > CP and controls; p < 0.05) and CD20+ lymphocytes (LAP/GAP > CP, p < 0.05 and LAP/GAP > controls; p < 0.001). Significant variations in the CD4+/CD8+ ratio were observed (LAP < controls and GAP < controls; p < 0.01), as well as a correlation between the number of T cells and the degree of inflammation. CONCLUSION: In the present study, patients with LAP and patients with GAP were found to have increased numbers of crevicular T-suppressor/cytotoxic and B cells. This supports the hypothesis of a changed immune pathology in patients with aggressive periodontitis.     

Personal risk factors for generalized periodontitis

Abstract Periodontitis is generally considered to be a consequence of an unfavourable host-parasite interaction in which bacteria are the determinants of disease. An intense search continues for the bacteria, specific or non-specfic, that are responsible for periodontitis and various forms of the periodontal diseases have been associated with, and are widely believed to be caused by, specific bacterial groups. However, the distribution of periodontopathic bacteria is far wider than the distribution of periodontitis, indicating that the association between bacteria and periodontitis is weak. This paper proposes a paradigm for the etiology of generalized periodontitis in which ‘host’ factors are not only those triggered by bacteria (the agent) but are also those personal factors that influence the outcome of the host/parasite relationship. The personal factors that diminish the efficiency of host defence may include psycho-social stress from the social environment, factors from the lifestyle such as diet, smoking and alcoholism and systemic factors such as intercurrent disease or deficiencies within the immune inflammatory system. A model is described in which the interaction of personal factors with the social environment provides the potential for the initiation of periodontitis. Biological variation is significant and the combination of factors that cause generalized periodontitis or any other chronic disease in one individual may not result in dental or any other chronic disease in another.     

Tooth-specific risk indicators for apical periodontitis

The present study aimed at identifying tooth-specific risk indicators for apical periodontitis (AP) and to investigate their interrelations in order to identify those teeth that would benefit from a radiographic examination. The study included 311 males and 302 females who gave written informed consent and attended a full-mouth radiographic examination. All teeth were assessed individually. AP was scored by the periapical index (PAI); other variables were root fillings, coronal fillings and crowns, pulpal posts, and caries. A conditional logistic regression analysis was used to assess the effect of tooth-specific risk indicators on the presence of apical periodontitis. The dependent variable was presence of AP versus absence of AP in the tooth. A total of 536 teeth with AP were identified. A highly increased risk for AP was seen in teeth with root fillings, particularly for technically inadequate ones. Presence of coronal fillings also increased the risk for AP, and inadequate fillings were associated with a slightly higher risk than adequate fillings. A similar pattern was seen for crowns. Teeth with caries also had an increased risk of AP, but the difference was only statistically significant for primary caries. Compared to first incisors, second incisors and canines had a significantly reduced risk, and molars, especially first maxillary molars, had a significantly increased risk for having AP.     

Socio-economic risk indicators for apical periodontitis

OBJECTIVE: The aim of this study was to reveal possible socio-economic risk indicators for apical periodontitis. MATERIAL AND METHODS: In 1992-93 a representative sample of women in G?teborg, Sweden, aged 38-84 years, participated in a medical and dental survey (n=981) which included dental and medical examinations and dental radiographic examination (OP). The dependent variable was apical periodontitis (AP=0, AP>0). The independent variables were age, number of teeth, number of restored teeth, number of root-filled teeth, number of teeth with carious lesions, satisfactory masticatory function, and dental esthetics as crude measures of self-reported dental health, dental anxiety, time elapsed since last visit to a dental office, regular dental visiting habits, smoking, alcohol habits, and marital status. A subjective evaluation of economy, health and life situation (acceptable or poor) was accounted for as socio-economic variables. The oldest age group, women born 1908, and edentulous individuals were omitted, leaving 844 subjects for analysis. Statistical analysis included multivariate logistic regression, chi-squared test, and independent t-test for comparison of group characteristics (AP=0 vs AP>0). RESULTS: For socio-economic variables there was a significant association between acceptable health and apical periodontitis (OR=1.72 (CI=1.09-2.70)). For oral-related variables, root-filled teeth (OR=1.17 (CI=1.10-1.23)) and teeth with carious lesions (OR=1.48 (CI=1.19-1.85)) were predictive of apical periodontitis. CONCLUSIONS: In the present study, socio-economic variables and dental visiting habits did not appear to have obvious implications for periapical health, whereas root-filled teeth and carious lesions were associated with apical periodontitis.     

Identification of genetic risk factors of aggressive periodontitis using genomewide association studies in association with those of chronic periodontitis

To identify the genetic risk factors for aggressive periodontitis (AgP), it is important to understand the progression and pathogenesis of AgP. The purpose of this review was to summarize the genetic risk factors for AgP identified through a case‐control genomewide association study (GWAS) and replication study. The initial studies to identify novel AgP risk factors were potentially biased because they relied on previous studies. To overcome this kind of issue, an unbiased GWAS strategy was introduced to identify genetic risk factors for various diseases. Currently, three genes glycosyltransferase 6 domain containing 1 (GLT6D1), defensin α1 and α3 (DEFA1A3), and sialic acid‐binding Ig‐like lectin 5 (SIGLEC5) that reach the threshold for genomewide significance have been identified as genetic risk factors for AgP through a case‐control GWAS.