Inducible Nitric Oxide Synthase Polymorphisms and Nitric Oxide Levels in Individuals with Chronic Periodontitis.

This study aimed to investigate whether the -1026(A>C)(rs2779249) and +2087(A>G)(2297518) polymorphisms in the NOS2 gene were associated with chronic periodontitis (CP) and with salivary levels of nitrite (NO2-) and/or nitrate + nitrite (NOx). A group of 113 mixed-race patients were subjected to periodontal, genetic, and biochemical evaluations (65 CP/48 periodontally healthy subjects). DNA was extracted from oral epithelial cells and used for genotyping by polymerase chain reaction (real-time). Salivary NOx concentrations were determined using an ozone-based chemiluminescence assay. Association of CP with alleles and genotypes of the -1026(A>C) polymorphism was found (X² test, p = 0.0075; 0.0308), but this was not maintained after multiple logistic regression, performed to estimate the effect of covariates and polymorphisms in CP. This analysis demonstrated, after correction for multiple comparisons, that only the female gender was significantly associated with CP. Polymorphisms analyzed as haplotypes were not associated with CP. NOx levels were significantly higher in the control group of heterozygous individuals for both polymorphisms. In conclusion, the female gender was significantly associated with CP, and higher levels of salivary NOx were found in control subjects and associated with the heterozygous state of the NOS2 polymorphisms, reinforcing the potential of NO metabolites as markers of periodontitis status.

Variation in the CXCR1 gene (IL8RA) is not associated with susceptibility to chronic periodontitis.

BACKGROUND: The chemokine receptor 1 CXCR-1 (or IL8R-alpha) is a specific receptor for the interleukin 8 (IL-8), which is chemoattractant for neutrophils and has an important role in the inflammatory response. The polymorphism rs2234671 at position Ex2+860G>C of the CXCR1 gene causes a conservative amino acid substitution (S276T). This single nucleotide polymorphism (SNP) seemed to be functional as it was associated with decreased lung cancer risk. Previous studies of our group found association of haplotypes in the IL8 and in the CXCR2 genes with the multifactorial disease chronic periodontitis. In this study we investigated the polymorphism rs2234671 in 395 Brazilian subjects with and without chronic periodontitis. FINDINGS: Similar distribution of the allelic and genotypic frequencies were observed between the groups (p>0.05). CONCLUSIONS: The polymorphism rs2234671 in the CXCR1 gene was not associated with the susceptibility to chronic periodontitis in the studied Brazilian population.

Haplotypes in the interleukin 8 gene and their association with chronic periodontitis susceptibility.

Interleukin-8 (IL-8), which is responsible for the migration and activation of neutrophils, is an important inflammatory mediator involved in the initiation and amplification of acute inflammatory reactions and chronic inflammatory processes. IL-8 plays an important role in periodontitis, an inflammatory disease characterized by the loss of connective tissue and alveolar bone. The aim of this study was to investigate whether the SNPs rs2227307 (+396) and rs2227306 (+781), and the haplotypes they formed together with the previously investigated rs4073 (-251), were associated with chronic periodontitis susceptibility. Clinical periodontal exams were performed and DNA samples were collected from 493 individuals (223 with periodontitis and 270 controls). Associations between SNPs, haplotypes, and subject phenotypes were analyzed using the χ(2) test followed by multivariate logistic regression modeling. We conclude that the +396TT genotype and the haplotypes ATC/TTC and AGT/TGC were significantly associated with chronic periodontitis susceptibility in Brazilians.

Polymorphisms and haplotypes in the interleukin-4 gene are associated with chronic periodontitis in a Brazilian population.

BACKGROUND: Some haplotypes in the interleukin-4 (IL4) gene were reported to influence IL-4 cytokine production and were associated with inflammatory diseases. Association studies focusing on IL4 gene polymorphisms and periodontal disease provided conflicting results. The aim of this study is to investigate whether IL4 gene polymorphisms and haplotypes were related to chronic periodontitis in a Brazilian population. METHODS: The polymorphisms -590(C/T) and +33(C/T) in the IL4 gene were identified by polymerase chain reaction (PCR) and restriction fragment-length polymorphism methods; the variable number of tandem repeats (VNTR) was identified by PCR. To assess the differences between the periodontitis group (n = 125) and control group (n = 125), the chi(2) test was used to assess genotype and allele distributions of individual polymorphisms. For haplotypes reconstructed by an expectation-maximization algorithm, the CLUMP program and Fisher exact test were used. Multivariate logistic regression modeling was used to assess the association of age, gender, smoking status, and polymorphism/haplotype with periodontitis. RESULTS: The -590(T), +33(C), and insertion (I) of 70-base pair (bp) alleles and genotypes were more prevalent in the periodontitis group, even after adjusting for covariates. The -590, +33, and insertion (TCI) haplotype was associated with a susceptibility to periodontitis (adjusted odds ratio [OR(adjusted)] = 2.68; 95% confidence interval [CI] = 1.50 to 4.80) as was the genotype TCI/CCI (OR(adjusted) = 5.27; 95% CI = 2.28 to 12.18), whereas the TTD (OR(adjusted) = 0.48; 95% CI = 0.26 to 0.91), CTI (OR(adjusted) = 0.28, 95% CI = 0.11 to 0.70), and TTD/CTI (OR(adjusted) = 0.29; 95% CI = 0.08 to 1.13) genotypes were a associated with protection against the development of chronic periodontitis. CONCLUSION: Significant associations between alleles, genotypes, and haplotypes of polymorphisms in the IL4 gene and chronic periodontitis were verified in Brazilian individuals.

Association of haplotypes in the CXCR2 gene with periodontitis in a Brazilian population.

CXCR-2 is a receptor of interleukin-8, which is involved in acute and chronic inflammatory processes. Polymorphisms in the CXCR2 gene have been associated with chronic inflammatory conditions. The aim of this study was to investigate whether the +785(C/T), +1208(T/C), and +1440(G/A) single-nucleotide polymorphisms (SNPs) in the CXCR2 gene, as well as their haplotypes, are associated with susceptibility to periodontitis in Brazilians. DNA was extracted from the buccal epithelial cells of 487 individuals (control = 215; periodontitis = 272). The SNPs were investigated using the sequence-specific primer-polymerase chain reaction method. Associations between the polymorphisms and subject phenotypes were analyzed using the chi-squared statistical test, followed by univariate and multivariate logistic regression modeling. Haplotypes were reconstructed using the expectation-maximization algorithm, and differences in haplotype distribution between the groups were analyzed to estimate genetic susceptibility for periodontitis development. Univariate and multivariate analysis revealed that age, skin color, and smoking status were associated with periodontitis. The +1440 GG genotype was shown to be protective against periodontitis in both univariate and multivariate analysis (odds ratio [OR](adjusted) = 0.42; 95% confidence interval [CI] = 0.19, 0.96). A similar relevant result for the +1440 GG was obtained in an alternative analysis considering a subgroup containing only white nonsmokers (OR = 0.37; 95% CI = 0.15, 0.92). White nonsmokers with the CTG/TCG haplotype appeared to be genetically protected against the development of periodontitis (OR = 0.29; 95% CI = 0.09, 0.89), while those carrying the CTG/TCA haplotype were more susceptible to the development of periodontitis (OR = 2.08; 95% CI = 1.24, 3.51). In conclusion, the +1440 SNP and some haplotypes are associated with periodontitis in Brazilian individuals.

Lack of association of a functional polymorphism in the interleukin 8 gene with susceptibility to periodontitis.

The important inflammatory mediator interleukin-8 (IL-8) is responsible for the migration and activation of neutrophils. The IL8 gene contains a functional single-nucleotide polymorphism (SNP) (rs4073) in its promoter region that may influence the expression of IL-8, and which has been associated with inflammatory diseases. The purpose of this study was to investigate the association of the SNP (rs4073) in the IL8 gene with susceptibility to periodontitis. DNA was extracted from the buccal epithelial cells of 500 individuals (control n = 224 and periodontitis n = 276). Individuals were genotyped for the SNP (rs4073) using sequence-specific primer polymerase chain reaction. Associations between the SNP (rs4073) and subject phenotypes were analyzed using the chi-squared test, followed by univariate and multivariate logistic regression modeling. The genotype distributions in both groups were consistent with Hardy-Weinberg equilibrium. Univariate and multivariate analysis showed that age, skin color, and smoking status were associated with periodontitis. No significant differences were found for sex and frequencies of alleles and genotypes between the control and periodontitis groups in the univariate analysis. These findings were replicated in the multivariate analysis. The SNP (rs4073) in the IL8 gene is not associated with susceptibility to periodontitis in Brazilian individuals, even after controlling for covariates.

A novel PCR-RFLP assay for the detection of the single nucleotide polymorphism at position +1440 in the human CXCR2 gene.

We designed a novel PCR-RFLP assay to genotype for the CXCR2 +1440 (G/A) single nucleotide polymorphism, which provides a simple, low-cost, practical, and reproducible method. Allele frequencies in healthy Brazilian individuals were found to be 0.65% for allele A and 0.35% for allele G.

Influência dos fatores genéticos na etiopatogênese da doença periodontal / Influences of genetic factors in the etipothogenesis of periodontal disease

A doença periodontal (DP) tem caráter multifatorial pois a infecção por microrganismos periodontopatogênicos que leva à inflamação e à destruição do periodonto é modulada pela resposta imune do hospedeiro, a qual é influenciada por hábitos como o fumo. Fatores relacionados ao hospedeiro no contexto da DP têm sido bastante estudados nos últimos anos, principalmente no que se refere à imunogenética, fato que motivou esta revisão da literatura, que teve como objetivo comentar a influência que fatores genéticos podem desempenhar na etiopatogênese da DP, dando ênfase aos polimorfismos genéticos. O levantamento bibliográfico foi realizado nas bases de dados Bireme e PubMed utilizando-se os termos “Periodontite, Genética e Polimorfismos”. Estudos sobre genética humana foram selecionados de forma a apresentar relação positiva ou negativa de fatores genéticos importantes, como polimorfismos, na DP. Concluiu-se pelos crescentes trabalhos na área que, apesar de ser inegável a influência genética na DP, ainda são necessários muitos outros estudos para melhor compreender esse mecanismo.

Periodontal diseases (PD) encompass multifactorial diseases due to the infection caused by periodontopathogenic microorganisms resulting in inflammation and periodontal destruction, are modulated by the host response. The immune response is influenced by host habits such as smoking. Important host factors regarding PD have been investigated in the last years, especially in immunogenetics. The aim of this literature review was to comment about genetic factors that might influence periodontal diseases. A search of Bireme and PubMed data bases was performed using terms like “Periodontitis, Genetics and Polymorphisms”. Important studies focusing on human genetics in individuals with periodontitis were selected to demonstrate positive and negative relationship between genetics factors, like polymorphisms, and PD. It can be concluded, considering the crescent number of studies in this area, that PD is influenced by genetic factors, although more researches are necessary to better understand which mechanisms are involved in this process.