Paula Cristina Trevilatto

The broad effects of the functional IL-10 promoter-592 polymorphism : modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome

Periodontal diseases are infectious diseases, in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. It occurs through the generation of metalloproteinases and the activation of bone resorption mechanisms. Anti‐inflammatory cytokines such as IL‐10 seem to attenuate periodontal tissue destruction through the induction of tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of osteoclastogenesis osteoprotegerin (OPG). A high individual variation in levels of IL‐10 mRNA is verified in periodontitis patients, which is possibly determined by genetic polymorphisms. In this study, the IL‐10 promoter ‐592C/A single nucleotide polymorphism (SNP), which is associated with a decrease in IL‐10 production, was analyzed by RFLP in 116 chronic periodontitis (CP) patients and 173 control (C) subjects, and the IL‐10, TIMPs, and OPG mRNA expression levels in diseased gingival tissues were determined by real‐time‐PCR. The IL‐10‐592 SNP CA (P=0.0012/OR=2.4/CI:1.4‐4.1), AA (P=0.0458/OR=2.3/CI:1.1‐4.9), and CA+AA (P=0.0006/OR=2.4/CI:1.4‐3.4) genotypes and the allele A (P=0.0036/OR=1.7/CI:1.2‐2.4) were found to be significantly more prevalent in the CP group when compared with control subjects. Both CA and AA genotypes were associated with lower levels of IL‐10, TIMP‐3, and OPG mRNA expression in diseased periodontal tissues and were also associated with disease severity as mean pocket depth. Taken together, the results presented here demonstrate that IL10‐592 SNP is functional in CP, being associated with lower levels of IL‐10 mRNA expression, which is supposed to consequently decrease the expression of the downstream genes TIMP‐3 and OPG, and influence periodontal disease outcome.

Failing Factors Associated With Osseointegrated Dental Implant Loss

Purpose:Dental implants are currently the aesthetic and functional alternative for tooth replacement. Despite the high success rate shown by longitudinal studies, failures do occur, even in patients who present appropriate clinical conditions. The aim of the present study was to identify factors related to, or determinant of, dental implant loss in patients of the Latin-American Dental Research Institute, Curitiba, PR, Brazil. Materials and Methods:Retrospective analysis of 3578 records of patients who had implants placed in this institute during the period of 1996 to 2006 was performed. Beyond records, panoramic and periapical radiographs were analyzed. Results:Of the 3578 individuals implant treated, failures occurred in 126 (3.5%) patients (mean age 52.2 ± 10.6 years). Men lost more implants (4.5%) than did women (3.1%) (P = 0.05). Most failure occurred before loading (88.2%). Failure was more frequent when the implant was installed in the posterior jaw (58.5%). The main detectable causes of implant loss were evaluated. Most implant losses (75%) did not have an apparent clinical cause. Identified causes were 17.5% iatrogenic conditions (surgical technique, contamination, and/or occlusal trauma), poor bone quality and quantity (3%), peri-implantitis (1%), and 3.5% missing data. Conclusions:The results obtained in this study suggest that host factors can be contributing to the failure of implants.

An Interleukin-1β (IL-1β) Single-Nucleotide Polymorphism at Position 3954 and Red Complex Periodontopathogens Independently and Additively Modulate the Levels of IL-1β in Diseased Periodontal Tissues

ABSTRACT Inflammatory cytokines such as interleukin-1β (IL-1β) are involved in the pathogenesis of periodontal diseases. A high individual variation in the levels of IL-1β mRNA has been verified, which is possibly determined by genetic polymorphisms and/or by the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans. In this study, we investigated the role of an IL-1β promoter single-nucleotide polymorphism at position 3954 [IL-1β(3954) SNP] and the presence of the periodontopathogens in the determination of the IL-1β levels in the periodontal tissues of nonsmoking chronic periodontitis (CP) patients (n = 117) and control (C) subjects (n = 175) and the possible correlations with the clinical parameters of the disease. IL-1β(3954) SNP was investigated by restriction fragment length polymorphism, while the IL-1β levels and the presence of the periodontopathogens were determined by real-time PCR. Similar frequencies of IL-1β(3954) SNP were found in the C and CP groups, in spite of a trend toward a higher incidence of T alleles in the CP group. The IL-1β(3954) SNP CT and TT genotypes, as well as P. gingivalis, T. forsythia, and T. denticola, were associated with higher IL-1β levels and with higher values of the clinical parameters of disease severity. Concomitant analyses demonstrate that IL-1β(3954) and the red complex periodontopathogens were found to independently and additively modulate the levels of IL-1β in periodontal tissues. Similarly, the concurrent presence of both factors was associated with increased scores of disease severity. IL-1β(3954) genotypes and red complex periodontopathogens, individually and additively, modulate the levels of IL-1β in the diseased tissues of nonsmoking CP patients and, consequently, are potentially involved in the determination of the disease outcome.

A critical review: an overview of genetic influence on dental caries

Dental decay is a complex, chronic disease and one of the most common illnesses in dentistry today. Several dental decay risk factors have been identified during the last years; however, these variables alone may not entirely explain the disease development. Genetic research applied to dental decay began in the 1930s with experimental reports in animals and human observational research. Only recently, have some studies begun to search for genetic polymorphisms in humans and apply linkage analysis. However, due to the complex characteristics of the disease, the strong influence from several biological and environmental factors, and the small number of genetic studies related to dental caries, the genetic basis still requires further study. Therefore, the aim of this review is to provide a brief description of the current methodology for genetic analysis of complex traits, followed by a comprehensive evaluation of the literature related to genetic susceptibility/resistance to dental decay and a discussion of different aspects of the applied methodology. Advances towards the elucidation of the dental decay genetic basis may contribute to the understanding of the disease etiopathogenesis and to the identification of high risk groups, thus providing potential targets for effective screening, prevention and treatment.

Enamel Formation Genes Influence Enamel Microhardness Before and After Cariogenic Challenge

There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes may contribute to caries. For the present study, we used DNA samples collected from 1,831 individuals from various population data sets. Single nucleotide polymorphism markers were genotyped in selected genes (ameloblastin, amelogenin, enamelin, tuftelin, and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Associations with caries experience can be detected but they are not necessarily replicated in all population groups and the most expressive results was for a marker in AMELX (p = 0.0007). To help interpret these results, we evaluated if enamel microhardness changes under simulated cariogenic challenges are associated with genetic variations in these same genes. After creating an artificial caries lesion, associations could be seen between genetic variation in TUFT1 (p = 0.006) and TUIP11 (p = 0.0006) with enamel microhardness. Our results suggest that the influence of genetic variation of enamel formation genes may influence the dynamic interactions between the enamel surface and the oral cavity.

Association between Vitamin D Receptor Gene Polymorphisms and Susceptibility to Chronic Kidney Disease and Periodontitis

Background/Aims: Chronic kidney disease (CKD) and periodontitis (PD) are serious public-health concerns. Vitamin D is a fat-soluble steroid hormone that interacts with its nuclear receptor (VDR) to regulate a variety of biological processes, such as bone metabolism, immune response modulation and transcription of several genes involved in CKD and PD disease mechanisms. The aim of this work was to investigate the association between polymorphisms in the VDR gene and end-stage renal disease (ESRD) and PD. Methods: 222 subjects with and without ESRD (in hemodialysis) were divided into groups with and without PD. Polymorphisms TaqI and BsmI in the VDR gene were analyzed by PCR restriction fragment length polymorphism. The significance of differences in allele, genotype and haplotype frequencies between groups was assessed by the χ2 test (p value <0.05) and odds ratio (OR). Results: Allele G was associated with protection against ESRD: groups without versus with ESRD (GG) × (GA+AA): OR = 2.5, 95% CI = 1.4–4.6, p = 0.00; (G × A): OR = 1.5, 95% CI = 1.0–2.3, p = 0.02; (TG + CG) × (TA + CA): OR = 1.5, 95% CI = 1.0–2.3, p = 0.02. No association was observed between the study polymorphisms and susceptibility to or protection against PD. Conclusion: Allele G of the VDR BsmI polymorphism was associated with protection against ESRD.

Analysis of the association between lactotransferrin (LTF) gene polymorphism and dental caries

Objective The present study evaluated the association between lactotransferrin (LTF) gene polymorphism (exon 2, A/G, Lys/Arg) and dental caries. Material and Methods A convenience sample of 110 individuals, 12 years old, was divided into: group 1, 48 individuals without caries experience (DMFT=0), and group 2, 62 subjects with caries experience (DMFT≥1). DNA was obtained from a mouthwash with 3% glucose solution, followed by a scrapping of the oral mucosa. After DNA purification, polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) was performed to access the study polymorphism. The LTF A/G (Lys/Arg) polymorphism had been previously reported as located in exon 1. Results Allele 1 of the study polymorphism was associated with low DMFT index and showed a protective effect against caries experience (OR=0.16, IC=0.030.76, p=0.01). Conclusion Lactotransferrin A/G (exon 2, Lys/Arg) polymorphism was associated with susceptibility to dental caries in 12-year-old students.

Tumor necrosis factor-alpha −308G/A single nucleotide polymorphism and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-α in diseased periodontal tissues

BACKGROUND AND OBJECTIVE Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177). MATERIAL AND METHODS The TNFA -308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction. RESULTS No statistically significant differences were found in the frequency of the TNFA -308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA -308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA -308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load. CONCLUSION Our results demonstrate that the TNFA -308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome.

Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians

UNLABELLED Chronic periodontal disease (PD) is an infectious immune-inflammatory illness. Polymorphisms in IL1 genes play a role in inflammatory diseases through the modulation of cytokine levels. OBJECTIVE this study aimed to investigate the association between polymorphisms in the IL1 gene cluster and chronic periodontitis in a Brazilian population. DESIGN a sample of 113 subjects over 25 years (mean age 41.2) were grouped into: 44 healthy individuals, 31 subjects with moderate and 38 with severe periodontitis. DNA was obtained through a mouthwash and oral mucosa scraping. PCR-RFLP was used to identify the following polymorphisms: IL1A C-889T (rs1800587), IL1B C-511T (rs16944), IL1B C+3954T (rs11436340), IL1RN intron 2 (rs2234663). Differences in the allele/genotype/haplotype frequencies were assessed by Chi-square test (p<0.05). The risk associated with alleles, genotypes and haplotypes was calculated as odds ratio (OR) with 95% confidence intervals (CI). RESULTS neither IL1A (C-889T) nor IL1B (C+3954T) polymorphisms was associated with chronic PD. Allele T for IL1B (C-511T) only associated with PD in the group of blacks and mulattos. Moreover, genotype 2/2 for IL1RN (intron 2) was associated with severe PD. CONCLUSIONS genotype 2/2 of IL1RN for the whole Brazilian population and allele T of IL1B (C-511T) in a subgroup of Afro-Americans and mulattos were suggested as putative risk indicators for chronic periodontitis.

Fresh-Frozen Bone Allografts in Maxillary Ridge Augmentation: Histologic Analysis

Bone allograft has become an alternative to autogenous bone due to its decreased operative trauma and the almost unlimited supply of reconstructive material. The aim of the present study was to histologically evaluate the suitability of fresh-frozen bone graft (test group) used in maxillary ridge augmentation, comparing it to autogenous bone (native maxilla: control group). During the re-entry procedures, 9 months after the fresh-frozen allogeneic bone blocks were placed in the atrophic maxillary ridges, bone cores were removed with a trephine bur from test and control treatments in the same patient. Routine histologic processing using hematoxylin and eosin and Picrosirius staining was performed. Mature and immature collagen area and density analysis were carried out for both groups under polarization. The results of Students t test for paired samples (P > .05) showed no statistically significant difference in mature and immature collagen area or density percentage between test and control groups. Histologically similar bone formation patterns were observed in both groups. We concluded that fresh-frozen bone allograft is a biologically acceptable alternative for augmentation of the deficient alveolar ridge, showing a similar collagen pattern to that of autogenous bone.