Determination of NLRP3 (rs4612666) and IL-1B (rs1143634) genetic polymorphisms in periodontally diseased and healthy subjects.

OBJECTIVE: The focus of the current study was to identify if a possible association between NLRP3 (rs4612666) and IL-1B (rs1143634) single-nucleotide polymorphisms (SNPs) may be implicated in the etiopathogenesis of chronic periodontitis (CP) in a Colombian population. DESIGN: One hundred and twenty-four CP subjects and 81 periodontally healthy controls (HC) were recruited. Periodontal status was assessed by criteria based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. Human genomic DNA was obtained from saliva samples of the study subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the NLRP3 (rs4612666) and IL-1B (rs1143634) SNPs. The association of polymorphisms with CP was assessed individually and adjusted for confounding using a multivariate binary logistic regression model. RESULTS: Bivariate analysis showed a weak association between CT genotype of NLRP3 (rs4612666) SNP and CP, however after logistic regression analysis, neither NLRP3 (rs4612666) nor IL-1B (rs1143634) polymorphisms were strongly/independently associated with disease status. Even so, an interaction effect was significantly detected not only among CT/CC genotypes of NLRP3 gene regarding to the age stratum ≥ 48 years, but also between CC genotype of the same gene and smoking habit. CONCLUSION: Although the present results do not support that IL-1B (rs1143634) SNP could be identified as a risk predictor for CP in the present population, the synergistic interaction of the CT/CC genotypes of NLRP3 (rs4612666) SNP with ageing and/or smoking habit potentially might play a significant role in the pathogenic pathways of periodontal disease.

Can periodontal infection induce genotoxic effects?

OBJECTIVE: This study aimed to evaluate the occurrence of chromosomal abnormalities, through micronuclei, and apoptosis by the sum of karyorrhexis, pyknosis and condensed chromatin in individuals with chronic periodontitis, gingivitis associated with biofilm and no periodontal disease. MATERIALS AND METHODS: This study included 72 individuals divided into three groups: gingivitis (n = 21), periodontitis (n = 24) and control (n = 27). Information on sociodemographic characteristics, health and lifestyle was obtained. Full mouth clinical examination was performed to define the periodontal condition. Exfoliated cells from gingival mucosa were collected for computation of micronuclei and nuclear changes indicative of apoptosis. The differences in the occurrence of endpoints (micronucleus, karyorrhexis, pyknosis and condensed chromatin) were evaluated using the conditional test to compare proportions in a rare events situation. RESULTS: There was no statistically significant difference in the occurrence of micronucleus (p > 0.1) between gingivitis, periodontitis and control groups. The occurrence of apoptosis was significantly higher among individuals with periodontitis compared to individuals with gingivitis (p < 0.05) and controls (p < 0.025). CONCLUSIONS: The findings showed that the inflammatory process generated by gingivitis and periodontitis is not related to a higher occurrence of chromosomal damage. However, the higher occurrence of apoptosis in individuals with periodontitis points to genotoxic effects induced by periodontal infection.

Association of CD28 and CTLA-4 gene polymorphisms with aggressive periodontitis in Brazilians.

OBJECTIVE: Susceptibility to and severity of periodontal disease is influenced by gene polymorphisms related to the immune response. Co-stimulatory molecules, such as CD28 and CTLA-4, are critical in the development of such responses. Our hypothesis is that polymorphisms in genes that code for these molecules may be associated with periodontitis. The aim of the study was to investigate the association between +17 (T/C) CD28 and +49 (A/G) CTLA-4 gene polymorphisms and periodontitis in Brazilians. MATERIALS AND METHODS: Genomic DNA was obtained from oral swabs of 424 individuals categorized into three groups (control group, aggressive, and chronic periodontitis) considering clinical parameters such as probing depth and clinical attachment loss. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There was an association between the T(-) genotype of the CD28 polymorphism and aggressive periodontitis (P = 0.04). Moreover, the A(+) genotype for CTLA-4 was associated with greater clinical attachment loss in non-smokers with aggressive periodontitis (P = 0.006, OR = 16.25, CI = 2.25-117.11). CONCLUSIONS: These findings show that T(-) in CD28 + 17 (T/C) and the A(+) in CTLA-4 +49 (A/G) genotypes are associated with susceptibility to aggressive periodontal disease. Thus, our study highlights these polymorphisms as potential genetic susceptibility markers of periodontitis in Brazilians.

MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression.

AIM: Matrix metalloproteinases (MMPs) play a key role in the tissue destruction characteristic of chronic periodontitis. The purpose of this study was to investigate the association of MMP and TIMP polymorphisms with chronic periodontitis in two populations. MATERIAL AND METHODS: A total of 34 polymorphisms spanning 12 MMP and 2 TIMP genes were genotyped in 401 individuals from Brazil (99 cases with chronic periodontitis and 302 controls), and 274 individuals from the US (70 cases and 204 controls). Individuals were considered cases if presenting at least three teeth exhibiting sites of clinical attachment loss ≥ 5 mm in two different quadrants. Controls were characterized by absence of clinical attachment loss and no sites with probing depth >3 mm. MMP3 and TIMP1 mRNA expression was evaluated in healthy and diseased periodontal tissues. RESULTS: TIMP1 showed association with chronic periodontitis in the Brazilian population (for rs5906435, p = 0.0004), whereas MMP3 showed association in the US population (for rs679620, p = 0.0003; and rs650108, p = 0.002) and in the Brazilian population (for rs639752, p = 0.005). MMP3 and TIMP1 mRNA expression was significantly higher in diseased tissues when compared to control tissues. CONCLUSIONS: Our results further support a role for variations in MMP3 in chronic periodontitis and report a novel association with TIMP1. These genes may be considered additional candidate genes for chronic periodontitis.

Periodontal disease in adults with untreated congenital growth hormone deficiency: a case-control study.

AIM: The aim of this study was to investigate the possible associations between isolated growth hormone deficiency (IGHD) and periodontal attachment loss (PAL) in adults affected by congenital IGHD. MATERIALS AND METHODS: Forty-five previously identified IGHD subjects were eligible for this study. The final study sample comprised 32 cases (gender:20M/12F; age:44.8 ± 17.5) matched for age, gender, diabetes, smoking status and income to 32 controls (non-IGHD subjects). Participants were submitted to a full-mouth clinical examination of six sites per tooth and were interviewed using a structured, written questionnaire. Periodontitis was defined as proximal PAL≥5 mm affecting ≥30% of teeth. RESULTS: No significant differences were observed in the percentage of sites with visible plaque between IGHD and non-IGHD subjects (59.4% versus 46.9%, p=0.32). IGHD subjects had significant less supragingival calculus (31.3% versus 59.4%, p=0.02) and more bleeding on probing (71.9% versus 18.8%, p<0.01) than controls. PAL≥5 mm was significantly more prevalent (100% versus 71.9%, p<0.01) and affected more teeth (30.5% versus 6.7%, p<0.01) in cases than in controls. After adjusting for supragingival calculus, IGHD cases had a higher likelihood of having periodontitis than controls (OR=17.4-17.8, 95% CI=2.3-134.9, p=0.004-0.005). CONCLUSION: Congenital IGHD subjects have a greater chance of having PAL.

Interleukin-6 (G-174C) and tumour necrosis factor-alpha (G-308A) gene polymorphisms in geriatric patients with chronic periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease, and genetic factors may have an important role in its severity. Polymorphisms in the promoter regions of the interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) genes have been reported to cause changes in the production of these cytokines. The aim of this study was to evaluate the possible role of IL-6 (G-174C) and tumour necrosis factor (G-308A) polymorphisms, in the severity of chronic periodontitis in an elderly population. MATERIALS AND METHODS: In this study, a group of 65 elderly women, comprising 17 patients with moderate chronic periodontitis, 21 with severe chronic periodontitis and 27 healthy patients were selected. DNA was isolated from all subjects, and polymerase chain reaction was used to study the IL-6 and TNF-alpha gene polymorphisms. RESULTS: The results of this study showed a significant difference in the allele and genotype frequencies of IL-6 gene polymorphism between patients with periodontal disease and controls. Subjects carrying the G/G genotype of IL-6 were most severely affected by periodontitis. The TNF-alpha gene polymorphism showed no association with chronic periodontitis between patients and controls. CONCLUSION: The results suggest that the IL-6 gene polymorphism may be associated with chronic periodontitis, and that TNF-alpha gene polymorphism may not be involved in the progression of chronic periodontitis in the population of elderly Brazilian women.

Interleukin-1 gene cluster polymorphisms associated with periodontal disease in type 2 diabetes.

BACKGROUND: Epidemiologic studies have shown an increased frequency, severity, and risk of periodontitis in patients with diabetes. Periodontitis is associated with certain interleukin (IL)-1 gene cluster polymorphisms. Diabetes is a proinflammatory state with increased levels of circulating cytokines suggesting a causal role for inflammation in its etiology. Common genetic factors may be involved in the susceptibility for diabetes and periodontitis. We evaluated the relationships among IL-1 gene polymorphisms, type 2 diabetes, and periodontitis. METHODS: One hundred twelve patients with diabetes and chronic periodontitis, 224 patients without diabetes but with chronic periodontitis, and 208 healthy subjects without periodontitis were studied. All received a clinical periodontal examination and assessment of standard periodontal parameters. IL-1A -889, -1B +3954, and -1B -511 polymorphisms were identified by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion and gel electrophoresis. Variable numbers of IL-1RN tandem repeats were detected by PCR amplification and fragment-size analysis. RESULTS: The severity and extent of periodontitis was significantly greater in patients with diabetes than in patients without diabetes. No significant differences in IL-1A -899, -1B +3954, or -1RN genotype frequencies were found between patients with diabetes and patients without diabetes. The IL-1A -889 TT genotype (odds ratio [OR] = 2.90; 95% confidence interval [CI] = 1.20 to 7.02), IL-1B +3954 TT genotype (OR = 3.54; 95% CI = 1.15 to 10.85), and IL-1B -511 CC genotype (OR = 2.10; 95% CI = 1.25 to 3.58) were significantly associated with periodontitis. The presence of an IL-1 positive genotype was significantly associated with periodontitis (OR = 1.61; 95% CI = 1.04 to 2.49). No interaction between smoking status and polymorphisms was found. CONCLUSIONS: Periodontitis was significantly associated with some IL-1 gene polymorphisms. No association between diabetes and IL-1A and -1B gene polymorphisms was found.

Polymorphism in the promoter region of the gene for 5-HTT in individuals with aggressive periodontitis.

Susceptibility to and development of periodontal disease have been associated with psychological conditions. Previous studies have associated the presence of polymorphism in the promoter region of the serotonin transporter with several behavioral traits and psychological conditions such as depression, anxiety, and stress. The short allele S has a reduced transcriptional efficiency and is associated with lowered serotonin expression and uptake. The purpose of the present study was to investigate the association between 5-HTTLPR polymorphism and aggressive periodontitis in a sample of Brazilian individuals. This study involved 61 individuals affected by aggressive periodontitis and 71 without periodontitis. Genomic DNA was obtained from oral swabs, amplified by polymerase chain reaction (PCR), and genotyped at 5-HTTLPR. The Chi-square test and multivariate logistic regression were used for statistical analysis. The aggressive periodontitis group displayed a significantly higher occurrence of genotype SS (P < 0.01) and of allele S (P < 0.01). After adjustment for gender and age, it was observed that genotype SS occurred 8 times more frequently in this group. Our findings suggest that 5-HTTLPR polymorphism might be associated with aggressive periodontitis in the Brazilian population.

Periodontal status of patients with dentin dysplasia type I: report of three cases within a family.

BACKGROUND: Dentin dysplasia type I (DDI) is a rare hereditary disturbance of dentin formation. It is characterized by clinically normal-appearing crowns; obliteration of pulp chambers; and short, blunted and malformed roots that are commonly associated with periodontal attachment loss (PAL). In this context, we report three cases within a family with similar clinical and radiographic features of DDI but with differing microbiologic and periodontal conditions. METHODS: A 42-year-old white female and her two daughters (25 and 10 years of age) presented with a diagnosis of DDI. Probing depth (PD), clinical attachment level (CAL), visible plaque, and bleeding on probing (BOP) were recorded. Subgingival biofilm samples were randomly collected and analyzed by checkerboard DNA-DNA hybridization. RESULTS: The mother presented 34.9% of sites with PD > or =4 mm, 41.3% of sites with CAL > or =4 mm, and 57% of sites with BOP; both daughters presented no sites with PD or CAL >3 mm and <10% of sites with BOP. Microbiologic analysis detected Gemella morbillorum, Neisseria mucosa, and Staphylococcus aureus in > or =50% of the mother's samples. The daughters showed high levels (>10(4) bacterial cells) of some periodontopathic bacteria, including members of the red (Porphyromonas gingivalis) and orange (Fusobacterium periodonticum and F. nucleatum polymorphum) complexes and beneficial species of the yellow (Streptococcus gordonii) and purple (Veillonella parvula) complexes. The mother presented high mean levels only for four tested species (N. mucosa, Prevotella melaninogenica, Treponema denticola, and V. parvula). CONCLUSION: A combination of radiographs, microbiologic analysis, and preventive professional monitoring care is important to avoid PAL and to provide oral health in patients with DDI.

Analysis of IL-1A(-889) and TNFA(-308) gene polymorphism in Brazilian patients with generalized aggressive periodontitis.

Generalized aggressive periodontitis (GAP) comprises a group of periodontal diseases characterized by the rapid destruction of periodontal tissues which affect young individuals who generally present no systemic disorders. Polymorphisms in the interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) genes have been associated with an increased severity of chronic periodontitis. The objective of the present study was to evaluate the association between IL-1A (-889) and TNFA (-308) gene polymorphisms and GAP. One hundred nonsmoking subjects were selected, including 30 with GAP and 70 without periodontal disease. Gene polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. For IL-1 (-889), the frequency of genotype 1/1 was 54.3% in the control group and 56.7% in the study group. The frequency of genotype 1/2 was 37.1% in the control group and 40% in the study group. Genotype 2/2 was detected at a frequency of 8.6% and 3.3% in the control and study groups, respectively. For TNFA, genotype 1/1 was present in 68.6% of control subjects and in 80.0% of patients with GAP, while the frequency of genotype 1/2 was 27.1% in the control group and 20% in the study group. Genotype 2/2 was present in 4.3% of control subjects and was not detected in the study group. The frequencies of allele 1 and allele 2 of the IL-1A (-889) gene were 72.9% and 27.1%, respectively, in the control group and 76.7% and 23.3% in the GAP group. For the TNFA (-308) gene, the frequency of allele 1 was 82.15% in the control group and 90% in the study group, whereas the frequency of allele 2 was 17.85% in the control group and 10% in the study group. Statistical analysis revealed no significant difference in allele distribution for either gene between the two groups. No association was observed between GAP and IL-1A (-889) and TNFA (-308) gene polymorphisms in Brazilian patients.

Genetic polymorphisms in the MMP-1 and MMP-3 gene may contribute to chronic periodontitis in a Brazilian population.

OBJECTIVES: Matrix metalloproteinase-1 and -3 (MMP-1, MMP-3) represent proteinases that degrade macromolecules of the extracellular matrix. These enzymes play a fundamental role during destruction of periodontal tissues. Genetic polymorphisms were characterized in the promoter region of the MMP-1 and MMP-3 genes. The aim of this study was to investigate the relationship between these genetic variations with chronic periodontitis in a Brazilian population. MATERIAL AND METHODS: Non-smoking subjects (n = 114) exhibiting sites > or = 5 mm clinical attachment loss were recruited for study. Control subjects (n = 109) should not exhibit clinical signals of periodontitis. MMP-1 (-1607 1G/2G, -519 A/G) and MMP-3 (-1612 5A/6A) gene promoter polymorphisms were genotyped using PCR-RFLP methods. RESULTS: Analysis of polymorphisms showed no differences in distribution of the -1607 1G/2G and -519 A/G variants in the MMP-1 gene between the healthy and periodontitis group (p > 0.05). However, the distribution of genotype frequencies of the -1612 5A/6A polymorphism in the MMP-3 gene showed that the 5A/5A genotype was significantly more frequent in the periodontitis group (p = 0.008). The same was not observed in the 5A/6A genotype once only one 5A allele is carried. We also observed a trend to increase the frequency of the MMP-1/MMP-3 haplotype (2G/5A) in the periodontitis group (p = 0.08). CONCLUSION: On the basis of the results, no significant association is found for the MMP-1 polymorphisms with susceptibility of periodontitis, while the MMP-3 gene polymorphism may contribute to periodontal tissue destruction during periodontitis in Brazilian subjects.

The effect of shared genetic and environmental factors on periodontal disease parameters in untreated adult siblings in Guatemala.

BACKGROUND: Increasing evidence supports the role of genetic factors in susceptibility to infectious diseases, including chronic periodontitis. The role of genetic factors in phenotypic expression can be estimated from the degree of resemblance between relatives, as compared with that of unrelated members of a population. Heritability is an estimate of the proportion of total phenotypic variation of a quantitative trait, which is attributable to genetic factors, and is based on the variance within versus between family members. The aim of this study was to determine whether there is a familial basis for periodontal disease status in an untreated population in Guatemala using heritability estimates as a measure of familial clustering of disease. METHODS: One-hundred and thirteen adult subjects (including both siblings and spouse pairs), age range 35 to 60 years, participated in this study. Full-mouth periodontal examinations were performed and heritability estimates were calculated for mean plaque score, mean gingival index (GI), probing depth (PD), and clinical attachment level (CAL). Intraclass correlation coefficients (ICCs) were calculated using the same parameters for spouses to determine whether a common family environment in adulthood plays a role in disease expression. RESULTS: Only in the case of mean plaque score and mean recession score were heritability estimates significantly above zero at alpha = 0.05. For spouse pairs, mean GI score, mean PD, and percentage of sites of PD > or = 5 mm showed a statistically significant ICC. CONCLUSIONS: These results lead us to reject the hypothesis that there is substantial heritability for periodontal disease expression in this population. This may be due to an underlying lack of genetic variation within this sample or may indicate that, compared with the role of environmental factors, the genetic contribution to periodontal disease phenotypes is relatively minor.