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Aim: Genetic polymorphisms (SNPs) in the interleukin-6 (IL-6) gene have been associated with the presence of periodontitis. The aim of this study was to investigate the association between five SNPs in the IL-6 promoter region and the periodontal status of a rural Indian population., Materials and Methods: Two hundred and fifty-one systemically healthy volunteers were clinically assessed by a single calibrated examiner and divided into: healthy individuals and periodontitis patients based on the European Workshop on Periodontitis definitions and on a recently suggested definition, which takes into account age and clinical attachment levels. Their genomic DNA was analysed blindly using real-time polymerase chain reaction to study IL-6 variants. The association between genetic factors and the presence of periodontitis was assessed by logistic regression., Results: The IL-6-174 GG genotype was associated with periodontitis in non-smokers and older subjects (>45 years old). No statistically significant associations were detected between IL-6 haplotypes and periodontal status, after adjusting for confounders., Conclusions: The IL-6-174 polymorphism showed some evidence of an association with the periodontal status in non-smokers and older subjects in this rural Indian population. This association might be mediated by the effect of IL-6 on inflammatory responses.

Aim: The aim of this analysis was to investigate the relationship between a vitamin D receptor (VDR) polymorphism and the diagnosis and progression of periodontitis., Material and Methods: Data were derived from two different studies, including 231 subjects with healthy periodontium, 224 aggressive periodontitis and 79 chronic periodontitis (CP) patients in a case-control investigation. Sixty-one of these CP patients also took part in an observational study with a 1-year follow-up, in which progression of periodontitis was determined at the subject level. All 534 subjects provided a blood sample from which genomic DNA was extracted to study VDR -1056 TaqI polymorphism., Results: The interaction between smoking and VDR polymorphism was associated with the diagnosis of periodontitis in Caucasians [p=0.001, odds ratio (OR)=1.33, 95% confidence intervals (CI)=1.12-1.57] and all subjects (p=0.033, OR=1.60, 95% CI=1.04-2.48). In the longitudinal study, subjects were divided into two clusters at 1 year according to the median number of progressing sites (Delta cumulative attachment loss >2 mm). Logistic regression analysis revealed that the interaction between VDR Taq-I polymorphism and smoking showed limited evidence of association with the "severe progression" cluster (p=0.033, OR=15.24, 95% CI=1.24-187.42)., Conclusions: Vitamin D receptor Taq-I TT polymorphism was moderately associated with both the presence and the progression of periodontitis in smokers, while no association was detected in non-smoking individuals. VDR genetic factors may interact with smoking in the pathogenesis of periodontitis.

Background: Growing evidence suggests that individual genetic susceptibility may influence the host's response to infections. Previously, we showed that a common variation in the interleukin (IL)-6 gene was associated with increased odds of detection of common periodontal pathogens from individuals with aggressive periodontitis. The aim of this study was to investigate the association between IL-6 polymorphisms and periodontopathogenic bacteria in a larger, ethnically mixed population of subjects with periodontitis., Methods: Genomic DNA was extracted from 107 subjects diagnosed with severe forms of periodontitis to study a cluster of polymorphisms in inflammatory genes, including IL-6. The presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T. forsythensis) in their subgingival biofilm was determined by polymerase chain reaction analysis. Serum IL-6 and C-reactive protein (CRP) concentrations were analyzed by enzyme-linked immunosorbent assay., Results: Multiple logistic regression analysis revealed that the IL-6 -6106 polymorphism was associated with the detection of A. actinomycetemcomitans (P = 0.009; odds ratio [OR] = 3.5; 95% confidence interval [CI]: 1.38 to 9.16) and the concomitant detection of A. actinomycetemcomitans and P. gingivalis (P = 0.015; OR = 3.6; 95% CI: 1.28 to 10.04). The IL-6 -174 polymorphism was associated with increased odds of the concomitant detection of A. actinomycetemcomitans and P. gingivalis (P = 0.042; OR = 2.8; 95% CI: 1.04 to 7.75). Haplotype analysis of all five IL-6 polymorphisms confirmed an association with the detection of A. actinomycetemcomitans (P = 0.046). The IL-6 -6106 polymorphism was also associated with CRP serum levels at multivariate analysis (P = 0.024)., Conclusions: These findings confirm the hypothesis that complex interactions between the microbiota and host genome are at the basis of susceptibility to periodontitis. Periodontal disease may represent a useful model to study the pathways and mechanisms of host-pathogen interactions in inflammatory diseases.

Background: Interleukin-6 (IL-6) polymorphisms have been shown to affect IL-6 promoter activity. This study investigated the possible role of IL-6 genetic polymorphisms and haplotypes in the predisposition to aggressive periodontitis (AgP)., Material and Methods: A case-control association study on 224 AgP patients and 231 healthy controls was performed in order to detect differences in genotype distributions of five single nucleotide polymorphisms (SNPs) located in the promoter region of the IL-6 gene., Results: The IL-6 -1363 polymorphism was associated with a diagnosis of AgP in subjects of all ethnicities (p=0.006, adjusted logistic regression). The -1480 SNP was associated with LAgP in subjects of all ethnicities (p=0.003). The -1480 and -6106 polymorphisms were associated with Localized AgP in Caucasians (n=24) (p=0.007 and 0.010, respectively). Haplotypes determined by the -1363 and -1480 polymorphisms were also associated with LAgP (p=0.001) in Caucasians., Conclusions: This study supports the hypothesis of a link between IL-6 genetic factors and AgP and highlights the importance of two IL-6 polymorphisms (-1363 and -1480) in modulating disease phenotype and susceptibility.

Objectives: The aim of this study was to assess the systemic effects of treating severe widespread periodontitis in a population of otherwise healthy individuals by examining treatment associated changes in markers of inflammation that are also implicated in cardiovascular atherosclerotic diseases. The potential impact of specific polymorphisms in cytokine genes known to influence both periodontitis and cardiovascular diseases was also examined., Materials and Methods: A convenience sample of patients affected with severe generalised periodontitis was enrolled into a prospective single blind longitudinal intervention trial with a 6 months follow-up. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assessed by high-sensitivity assays. Serological and clinical periodontal parameters were evaluated at baseline, 2 and 6 months after completion of non-surgical periodontal therapy., Results: In the 94 subjects that completed this pilot trial improvements in all clinical periodontal parameters were achieved. These were accompanied with significant reductions in serum IL-6 and CRP concentrations. In a multivariate model, serum CRP levels were significantly associated with the outcome of periodontal treatment after correcting for potential covariates (age, body mass index, gender, smoking) and polymorphisms in the IL-6 (-174 C/G) and IL-1A (-889) genes. A median decrease in serum CRP of 0.5 mg/l (95% CI 0.4-0.7 mg/l) was observed 6 months after completion of periodontal therapy in this population. Subjects with above average response to periodontal therapy (<30 residual pockets and <30% of sites bleeding on probing) accounted for the observed improvement in serum CRP., Conclusions: Control of periodontitis, achieved with non-surgical periodontal therapy, significantly decreased serum mediators and markers of acute phase response. The significance of the serum response was associated with the half of the population that responded better to non-surgical periodontal therapy. The results of this pilot study indicate that severe generalised periodontitis causes systemic inflammation. This is consistent with a causative role of periodontitis in atherogenesis.

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon-Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early-onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 micro moles/mg/min vs. 1,678.7 +/- SD 527.2 micro moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS., (Copyright 2004 Wiley-Liss, Inc.)

Aim: The aim of this analysis was to investigate the relationship between a vitamin D receptor (VDR) polymorphism and the diagnosis and progression of periodontitis. Material and Methods: Data were derived from two different studies, including 231 subjects with healthy periodontium, 224 aggressive periodontitis and 79 chronic periodontitis (CP) patients in a case–control investigation. Sixty-one of these CP patients also took part in an observational study with a 1-year follow-up, in which progression of periodontitis was determined at the subject level. All 534 subjects provided a blood sample from which genomic DNA was extracted to study VDR −1056 TaqI polymorphism. Results: The interaction between smoking and VDR polymorphism was associated with the diagnosis of periodontitis in Caucasians [ p=0.001, odds ratio (OR)=1.33, 95% confidence intervals (CI)=1.12–1.57] and all subjects ( p=0.033, OR=1.60, 95% CI=1.04–2.48). In the longitudinal study, subjects were divided into two clusters at 1 year according to the median number of progressing sites (Δcumulative attachment loss >2 mm). Logistic regression analysis revealed that the interaction between VDR Taq-I polymorphism and smoking showed limited evidence of association with the “severe progression” cluster ( p=0.033, OR=15.24, 95% CI=1.24–187.42). Conclusions: Vitamin D receptor Taq-I TT polymorphism was moderately associated with both the presence and the progression of periodontitis in smokers, while no association was detected in non-smoking individuals. VDR genetic factors may interact with smoking in the pathogenesis of periodontitis. [ABSTRACT FROM AUTHOR]