Valquiria Quinelato

Genome wide association scan for chronic periodontitis implicates novel locus

BackgroundThere is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).MethodsGenotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.ResultsThe rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.ConclusionsOur data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis.

BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes

OBJECTIVES To investigate whether genetic variants can be correlated with tendinopathy in elite male volleyball athletes. DESIGN Case-control study. METHODS Fifteen single nucleotide polymorphisms within BMP4, FGF3, FGF10, FGFR1 genes were investigated in 138 elite volleyball athletes, aged between 18 and 35 years, who undergo 4-5h of training per day: 52 with tendinopathy and 86 with no history of pain suggestive of tendinopathy in patellar, Achilles, shoulder, and hip abductors tendons. The clinical diagnostic criterion was progressive pain during training, confirmed by magnetic resonance image. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped using TaqMan real-time PCR. Chi-square test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of covariates and incidence of tendinopathy. RESULTS Statistical analysis revealed participant age (p=0.005) and years of practice (p=0.004) were risk factors for tendinopathy. A significant association between BMP4 rs2761884 (p=0.03) and tendinopathy was observed. Athletes with a polymorphic genotype have 2.4 times more susceptibility to tendinopathy (OR=2.39; 95%CI=1.10-5.19). Also, association between disease and haplotype TTGGA in BMP4 (p=0.01) was observed. The FGF3 TGGTA haplotype showed a tendency of association with tendinopathy (p=0.05), and so did FGF10 rs900379. FGFR1 showed no association with disease. CONCLUSIONS These findings indicate that haplotypes in BMP4 and FGF3 genes may contribute to the tendon disease process in elite volleyball athletes.

Haplotypes of the RANK and OPG genes are associated with chronic arthralgia in individuals with and without temporomandibular disorders

The aim of this study was to evaluate the association between genetic polymorphisms and the comorbid presence of chronic systemic arthralgia in patients with articular temporomandibular disorders (TMD). Subjects were evaluated for the presence of TMD and asked about the presence of chronic joint pain. Four groups were included in the study: articular TMD and systemic arthralgia (n=85), no articular TMD and systemic arthralgia (n=82), articular TMD and no systemic arthralgia (n=21), no articular TMD and no systemic arthralgia (control, n=72). A total of 14 single nucleotide polymorphisms in the OPG, RANK, and RANKL genes were investigated. In the statistical analysis, a P-value of <0.05 was considered significant. For the OPG gene, an association was observed between the group with chronic arthralgia and joint TMD and the control group (P=0.04). There was also a tendency towards an association of the haplotype CGCCAA with an increased risk of developing chronic joint pain, even in the absence of TMD (P=0.06). For the RANK gene, the AGTGC haplotype was associated with the lowest risk of presenting chronic joint pain in individuals without TMD (P=0.03). This study supports the hypothesis that changes in the OPG and RANK genes influence the presence of chronic joint pain in individuals with and without TMD.

MMP13, TIMP2 and TGFB3 Gene Polymorphisms in Brazilian Chronic Periodontitis and Periimplantitis Subjects

Subjects susceptible to chronic periodontitis (CP) show a high risk for the development of periimplantitis (PI). Both diseases are multifactorial, presenting similarities in their pathophysiology and polygenic profile. MMP-13 (matrix metalloproteinases 13/ collagenase 3) is a collagenolytic enzyme, which expression is induced by TGF beta 3 (transforming growth factor type 3) in human gingival fibroblasts and inhibited by TIMP-2 (tissue inhibitor of metalloproteinase type 2). The aim of this study was to investigate the occurrence of periimplantitis (PI) in subjects with history of chronic periodontitis (CP) and polymorphisms frequency in MMP13, TIMP2 and TGFB3 genes. One hundred and sixty-three volunteers received dental implant placement were submitted to oral and radiographic examination in order to identify past history of CP or presence of PI. Volunteers were divided into 4 groups: Control (without PI and CP, n=72), CP (with CP and without PI, n=28), PI (with PI and without CP, n=28) and diseased (with CP and PI, n=35). The chi-square test correlated genotypes in specific regions of MMP13 (rs2252070), TIMP2 (rs7501477) and TGFB3 (rs2268626) genes, considering the interaction between CP and PI. The results showed that volunteers with CP had 3.2 times more susceptibility to develop PI (p=0.0004) compared to those without CP. No significant association was observed in MMP13, TIMP2 and TGFB3 genes with CP or PI. CP is a risk factor to develop PI, however, there is no association of both diseases with polymorphisms in the MMP13, TIMP2 and TGFB3 genes.

Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation

tHistory of chronic periodontitis (CP) is a risk factor for oseointegration failure. The osteoclastogenesis system (RANK, RANKL and OPG) is critical for bone homeostatic control. We investigated the levels of OPG and RANKL in peri-implant tissues from volunteers with and without a history of CP and their association with mucosae inflammation. This is a single-blind case-contro study. Diagnosis of a history of CP and peri-implant examination was performed on 46 volunteers, divided into control (without history of CP, n=26) and CP group (with history of CP, n=20). Gingival biopsies were harvested during implant exposure. Quantitative PCR evaluated OPG/RANKL mRNA expressions. OPG and RANKL proteins were analyzed by western blot and immunohistochemistry assay. The chi-square test analyzed the significance of nominal variables between groups while continuous variables were analyzed by T-test or Mann-Whitney test, after Shapiro-Wilk test evaluation. The 2-ΔΔCT Livak method calculation evaluated the gene expression. Values of p<0.05 were considered statistically significant. Volunteers with CP history had 23 times higher chance of developing mucosae inflammation. High mucosae levels of RANKL (p=0.04) and RANKL/OPG (p=0.001) mRNA expressions were observed in CP group. CP volunteers showed increased RANKL protein levels in opposition to decreased OPG expression. Even without active periodontitis, volunteers with a history of CP had elevated gingival levels of RANKL/OPG and higher correlation with peri-implant mucosae inflammation and implant loss.

Haplotypes in BMP4 and FGF Genes Increase the Risk of Peri-Implantitis

Despite the success of osseointegrated implants, failures have increased significantly, associated with development of peri-implantitis. Multiple factors influence the peri-implant bone loss, including environmental and genetic causes. BMPs (Bone morphogenetic proteins) are growth factors that induce bone formation. FGF (fibroblast growth factors) and their receptors (FGFRs) play important roles by controlling the levels of cell proliferation, differentiation and migration. BMP/FGF relationship is responsible for promoting bone regeneration and bone loss. The aim of this study was to analyze the correlation between BMP4, FGF3, FGF10 and FGFR1 genes and peri-implant bone loss. Two hundred and fifteen volunteers, with 754 dental implants, were submitted to oral examination and divided in healthy group (n=129) and peri-implantitis group (n=86). Thirteen polymorphisms in BMP4, FGF3, FGF10 and FGFR1 genes were analyzed individually and in haplotype. The chi-square test correlated genotypes, allelic and haplotype frequencies. Values of p<0.05 were considered significant. Volunteers with peri-implantitis demonstrated high incidence of total edentulism (p<0.0001) and thin peri-implant phenotype (p<0.04). Higher incidence of spontaneous bleeding, plaque and implant mobility was observed in peri-implantitis group (p<0.0001 for all). The TT polymorphic genotype for BMP4 rs2761884 was associated with healthy peri-implant (p=0.01). FGF3 rs4631909 (TT+CT genotype) also showed association with the control group (p=0.04). The frequency of C allele for FGF3 rs4631909 showed a tendency for association with peri-implantitis (p=0.08). FGF10 CCTG (p=0.03), BMP4 GAAA (p=0.05) and GGGA (p=0.02) haplotypes were associated with peri-implantitis (p=0.03). Therefore, it may be concluded that BMP4 and FGF10 haplotypes are associated with peri-implantitis.

Bruxismo: uma abordagem genética

O bruxismo e definido como uma atividade repetitiva dos musculos mastigatorios caracterizada pelo ranger e/ou apertar de dentes com diferentes manifestacoes circadianas. Devido a complexidade da condicao e a variedade de disturbios associados ressalta-se a necessidade de um conhecimento detalhado sobre possiveis fatores individuais a fim de direcionar a conduta especifica para consequencias do bruxismo. A obtencao de dados genetico-moleculares para estudo da possivel relacao entre genetica e bruxismo acarretaria em um melhor diagnostico e tratamento dos bruxomanos. Dessa forma, o presente estudo buscou elucidar essa relacao por meio de uma revisao de literatura. Estudos atuais mostraram indicios da influencia de genes da via dopaminergica e seratoninergica no desenvolvimento do bruxismo. Com base em relacoes que possam existir entre fatores geneticos e a origem da condicao, mostra-se necessaria a ampliacao do campo de pesquisa genetica-molecular no objetivo de elucidar mecanismos associados e/ou desencadeantes da parafuncao, possibilitando diagnosticos e tratamentos precisos.

Dental genetics in Brazil: Where we are

Dentistry constitutes the basic nucleus of professionals of higher level of health in Brazil with one of the largest concentrations of dentists per capita in the world. However, the genetic in dentistry in Brazil is explored, basically, in research field. Future actions need to be performed in order to deep the whole knowledge about diagnosis and treatment of diseases with genetic basis in dentistry, in Brazil.

Peri-implant mucosae inflammation during osseointegration is correlated with low levels of epidermal growth factor/epidermal growth factor receptor in the peri-implant mucosae

Peri-implant mucosae inflammation during osseointegration period can promote host response imbalance and bone resorption by bacteria infiltration. Aim: To evaluate the association between EGF and EGFR gene expressions in the peri-implant tissue with mucosae inflammation during osseointegration period. Material and Methods: Forty-nine participants, with 59 endosseos implants, were recruited for this study. All participants included were rehabilitated with implants in two stages surgical protocol, presenting favorable bone quality and quantity. Osseointegration was evaluated one month after exposure surgery, wich was performed three months (mandible) and 6 months (maxillary) after implant placement. The criteria to consider the proper osseointegration were: Implant immobility; absence of peri-implant radiolucency; and no clinical signs of inflammation. Based on clinical and radiographic characteristics of peri-implant sites, participants were characterized as (i) having healing without complications (with proper osseointegration without mobility of the implant, and without clinical signs of mucosal inflammation) (control group) or (ii) failure peri-implant healing (with inadequate osseointegration characterized by signs of mucosae inflammation and/or implant mobility) (test group). Gingival biopsies were collected from 49 participants after osseointegration period, during the exposure procedure. Total RNA from gingival samples was isolated using the Trizol® reagent. The reaction of reverse transcription of PCR was performed for the synthesis of complementary DNA from 300ng RNA using Improm-II Reverse Transcription System™. Specific primers for EGF (NM_001963.4) and EGFR (NM_005228.3) were based on the BLAST data. The Livak method (2-ΔΔCT) was used to determine the relative quantification of the expression of EGF and EGFR. The values were normalized by relative expression of β-actin. Results: There was no difference between control and test groups to race, sex, age, alcohol consumption, general medical conditions, current medications, edentulism and periodontal phenotype. All RNA samples revealed proportions A260 nm/A280 nm more than 1.9. EGF and EGFR showed significant lower expression in gingival tissues removed from regions with failure healing (test group). EGF showed mRNA expression with an average of 44.53 ± 79.16 and 01.02 ± 1:33 in the control groups and test, respectively (P = 0.008). Similarly EGFR expression was significantly higher in the control group (102.03 ± 329.57) compared to the test group (7.85 ± 4.16) (P = 0:04). Conclusion: Low levels of EGF and EGFR are associated with inadequate healing of mucosal peri-implant during the osseointegration period.