RANK/RANKL/OPG gene polymorphisms and loss of orthodontic mini-implants.

OBJECTIVE: To investigate the association of genetic polymorphisms (tagSNPs type) of RANK/RANKL/OPG genes with the loss of orthodontic mini-implants (MIs). SETTING AND SAMPLE POPULATION: One hundred and thirty-five patients of both sexes, with mean age of 48.7 ± 10 (20-76 years), were studied. The control group was composed of 104 patients, with no MI lost and functioning for at least 6 months and the case group, of 31 patients with at least one MI lost. MATERIALS AND METHODS: Cells were obtained by mouthwash with 3% glucose solution for 1 minute and scraping the buccal mucosa with sterilized spatula. DNA was extracted from buccal epithelial cells with 10 M ammonium acetate and 1 mM EDTA. Genotyping was performed by the real-time polymerase chain reaction (PCR) technique. Univariate and multivariate analyses were performed (P < .05). RESULTS: No markers were associated with MI loss after Benjamini and Hochberg false discovery rate correction of Univariate tests. In the multivariate analysis, the variables that associated with MI loss were the number of MIs installed (P < .000) and the polymorphism rs8086340 in the RANK gene (P = .018). CONCLUSION: A higher number of MIs installed (P < .000) and polymorphism rs8086340 in the RANK gene (P = .018) were associated with loss of orthodontic MIs after multivariate analysis.

A complete physical mapping of the vitamin D receptor gene for dental implant loss: A pilot study.

OBJECTIVES: The aim of this pilot case-control study was to investigate the association of clinical variables and genetic polymorphisms in the vitamin D receptor gene (VDR) with dental implant loss. MATERIAL AND METHODS: This study was carried out with 244 individuals with mean age 51.90 ± 11.28 (81 cases and 163 controls matched by age, sex, and smoking habit). Also, the clusterization phenomenon was investigated stratifying the sample into two groups: (a) 34 patients with multiple losses (presenting two or more lost implants) and (b) 210 without multiple losses (up to one implant loss). Sociodemographic, clinical, and periodontal parameters were analyzed. The tagSNPs in the VDR gene were analyzed by real-time PCR. Univariate and multivariate analyses were performed (p < .05). RESULTS: Edentulism, number of implants installed, and Gingival, Plaque, and Calculus Indexes were associated with implant loss in the univariate analysis. After the multivariate analysis, the allele G of rs3782905 in the recessive model, together with number of installed implants and Gingival Index, was associated with implant failure. CONCLUSION: It is suggested that the allele G of rs3782905 in the recessive model may be a new genetic risk marker for dental implant loss in patients who lost two or more dental implants. In addition, number of implants installed and Gingival Index were also associated. Replication is mandatory to confirm these findings, due to the modest sample size of this work.

Association of clinical variables and polymorphisms in RANKL, RANK, and OPG genes with external apical root resorption.

OBJECTIVES: The aim of this study was to investigate the association of clinical variables and polymorphisms in the RANKL, RANK, and OPG genes with external apical root resorption (EARR). METHODS: The sample was composed of 338 unrelated patients of both sexes, average age 14.9 years (range 8-21) with Class II Division 1 malocclusion, orthodontically treated. Periapical radiographs of the maxillary central incisor with the longer root (reference tooth) were taken before treatment and 6 months after starting treatment. DNA was extracted from buccal epithelial cells with the use of 10 mol/L ammonium acetate and 1 mmol/L EDTA. The analysis of 42 polymorphisms in the RANKL, RANK, and OPG genes was performed by means of real-time polymerase chain reaction. Univariate and multivariate analyzes were performed to verify the association of clinical and genetic variables with EARR (P <0.05). RESULTS: The initial root length and patient age were associated with EARR. Considering the study of polymorphisms of RANKL, no significant association was found of genetic polymorphisms with EARR. For RANK polymorphisms, only rs12455775 was associated with EARR. Regarding OPG polymorphisms, an association of rs3102724, rs2875845, rs1032128, and rs3102728 with EARR was found. After multivariate analysis, the initial root length, rapid maxillary expansion, and rs3102724 of the OPG gene were associated with EARR. CONCLUSIONS: Longer roots of upper central incisors and rapid maxillary expansion, as well as allele A of the rs3102724 polymorphism of the OPG gene, were associated with EARR in the study population.

Polymorphisms in Nonamelogenin Enamel Matrix Genes Are Associated with Dental Fluorosis.

The aim of this study was to evaluate whether genetic polymorphisms in AMELX, AMBN, ENAM, TFIP11, and TUFT1 genes are associated with dental fluorosis (DF). A total of 1,017 children from 2 Brazilian cohorts were evaluated. These populations lived in cities with fluoridation of public water supplies. DF was assessed in erupted permanent teeth using the modified Dean index. The polymorphisms rs946252, rs12640848, rs4694075, rs5997096, and rs4970957 were analyzed by real-time PCR from genomic DNA. Associations between DF, genotype, and allele distribution were evaluated using the χ2 test, with an alpha of 5%. The polymorphisms rs4694075, rs5997096, and rs4970957 in AMBN, TFIP11, and TUFT1 were associated with DF (p < 0.05). In conclusion, enamel matrix genes are associated with DF.

Genes Involved in the Enamel Development Are Associated with Calcium and Phosphorus Level in Saliva.

Saliva components play a crucial role in the integrity of the dental enamel and in caries susceptibility. The saliva characteristics are controlled by many factors, including genetic factors. Therefore, this study aimed to evaluate the association between the genetic variations in genes expressed in enamel development with calcium and phosphorus levels in saliva. We collected 276 unrelated 12-year-old children from private and public schools. Saliva was collected for DNA extraction from oral cells and for measurement of calcium and phosphorus. Inductively coupled plasma-mass spectrometry determined calcium and phosphorus levels in whole saliva. Fifteen genetic variations in 9 genes were analyzed. The genotype was determined by real-time polymerase chain reactions. Data were analyzed using Plink with an alpha of 5%. Genetic variations in AMELX, AMNB and ESRRB were associated with the calcium level in saliva (p < 0.05). A borderline association was observed in ENAM allele distribution shown with phosphate level in saliva (p = 0.049). In conclusion, our results are the first to report that genetic variations contribute to calcium and phosphorus levels in saliva.

Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning.

OBJECTIVE: The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions. DESIGN: Cross sectional study. SETTING: Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013. SUBJECTS: The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99). METHODS: The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene. RESULTS: The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS. CONCLUSION: These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS.

Lactotransferrin Gene Polymorphism Associated with Caries Experience.

Dental caries is a common multifactorial disease, resulting from the interaction of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF) is a main salivary glycoprotein, which modulates the host immune-inflammatory and antibacterial response. Although a genetic component for caries outcome has been identified, little is known over the genetic aspects underlying its susceptibility. Thus, the aim of this study was to investigate the association between LTF polymorphisms and caries susceptibility. Six hundred seventy seven 12-year-old students were selected: 346 with (DMFT ≥ 1) and 331 without caries experience (DMFT = 0). Also, individuals concentrating higher levels of disease (polarization group, DMFT ≥ 2, n = 253) were tested against those with DMFT ≤ 1 (n = 424). Along with clinical parameters, three representative LTF tag SNPs (rs6441989, rs2073495, rs11716497) were genotyped and the results were evaluated using univariate and multivariate analyses. Allele A for tag SNP rs6441989 was found to be significantly less frequent in the polarization group, conferring a protective effect against caries experience [AA + AG × GG (OR: 0.710, 95% CI: 0.514-0.980, p = 0.045)], and remained significantly associated with caries protection in the presence of gingivitis (p = 0.020) and plaque (p = 0.035). These results might contribute to the understanding of the genetic control of caries susceptibility in humans.

FasL expression in articular discs of human temporomandibular joint and association with osteoarthrosis.

BACKGROUND: Apoptosis is a programme of cell death which does not induce an inflammatory response. Recent previous research has suggested a correlation between temporomandibular internal derangement and apoptosis. Fas ligand (FasL) is an apoptosis-inducing factor, known to trigger apoptosis through distinct signal pathways. This study aims to examine, by immunohistochemistry, the expression of FasL in temporomandibular joint (TMJ) articular discs of patients with anterior disc displacement with reduction (ADDwR) and without reduction (ADDwoR) in patients with and without osteoarthrosis (OA). METHODS: Forty-two (n = 42) TMJ articular discs were divided into two cut-offs: (i) 8 control, 17 ADDwR, 17 ADDwoR, and (ii) without OA (n = 25) and with OA (n = 17). The area of immunostaining was compared statistically between groups (P < 0.05). RESULTS: Statistically significant differences were found in the expression of FasL in TMJ discs between the three groups (P = 0.001). ADDwR presented significant higher FasL expression when compared with ADDwoR (P < 0.001). Significant higher FasL expression was observed in the group without OA (P = 0.001). All patients without OA presented ADDwR, while all the patients with OA presented ADDwoR. CONCLUSION: A higher area of in situ immunostaining of FasL was found in temporomandibular discs with reduction, which is the less severe condition. Moreover, a reduced expression of FasL in the discs of patients with osteoarthrosis was found, suggesting that some aspects of apoptosis might underlie the progression of TMJ disorders.

3D printing feasibility of a controlled dynamization device for external circular fixation.

AIM: to assess the small-scale 3D printing feasibility and cost estimation of a device for controlled dynamization. MATERIALS AND METHOD: The two-part device previously developed by our research group was printed with a carbon fiber-reinforced nylon filament (Gen3 CarbonX™ PA6+CF, 3DXTECH Additive Manufacturing) by a professional 3D printer (FUNMAT HT, Intamsys). Electricity, material, and labor costs for production in a Brazilian city in the Santa Catarina state were calculated. RESULTS: The devices for controlled dynamization were successfully printed in accordance with the planned design and dimensions. Six out of 38 printed devices presented defects in the bolt hole and were discarded. The average printing time per device was 1.9 h. The average electricity, material, and labor costs per printed device were respectively US$0.71, US$13.55, and US$3.04. The total production cost per device reaches approximately US$20 by adding the average cost of defective devices (15 %). CONCLUSION: 3D printing of the controlled dynamization device is feasible and its cost seems affordable to most healthcare services, which could optimize the consolidation of diaphyseal fractures and reduce treatment time for patients.

Analysis of IL1 gene polymorphisms and transcript levels in periodontal and chronic kidney disease.

UNLABELLED: Chronic kidney disease (CKD) and periodontitis (PD) are complex inflammatory disturbances, influenced by genetic factors. Interleukin (IL)-1 genes code for inflammatory mediators involved in the physiopathogenesis of both diseases. Functional polymorphisms in IL1 genes modulate cytokine levels and have been associated with susceptibility to immune-inflammatory conditions. OBJECTIVES: The aim of this study was investigate the association of functional IL1 gene polymorphisms and transcript levels with susceptibility to CKD and PD. DESIGN: The sample consisted of 246 individuals, mean age 44.8 years, divided into: group 1 (64 patients without CKD and without PD), group 2 (58 without CKD and with PD), group 3 (52 with CKD and without PD) and group 4 (72 with CKD and with PD). DNA was obtained from cells of oral mucosa and polymorphisms IL1AC-889T, IL1BC-511T, IL1BC+3954T and IL1RN (intron 2) were analyzed by PCR-RFLP. Transcript levels from gingival tissues were analyzed by real-time PCR. RESULTS: IL1RN(*)1 allele was associated with almost 4-fold increased risk for CKD (OR 3.92 95% CI=1.6-9.4, p=0.002). IL1RN(*)2 allele was associated with 3-fold increased risk for PD in CKD patients (OR 3.08 95% CI=1.2-7.9, p=0.019). Allele T for polymorphism IL1B+3954 was associated with CKD in PD patients (OR 2.28 95% CI=1.1-4.7, p=0.019). Significantly increased levels of transcripts of IL1A, IL1B and IL1RN genes were found in PD patients. CONCLUSIONS: It was observed an evidence for association of IL1B and IL1RN alleles with susceptibility to CKD and PD. Higher levels of IL1 gene transcripts were found in PD patients.

Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients.

INTRODUCTION: Vitamin D is responsible for the regulation of certain genes at the transcription level, via interaction with the vitamin D receptor, and influences host immune responses and aspects of bone development, growth, and homeostasis. Our aim was to investigate the association of TaqI vitamin D receptor gene polymorphism with external apical root resorption during orthodontic treatment. METHODS: Our subjects were 377 patients with Class II Division 1 malocclusion, divided into 3 groups: (1) 160 with external apical root resorption ≤1.43 mm, (2) 179 with external apical root resorption >1.43 mm), and (3) 38 untreated subjects. External apical root resorption of the maxillary incisors was evaluated on periapical radiographs taken before and after 6 months of treatment. After DNA collection and purification, vitamin D receptor TaqI polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism. Univariate and multivariate analyses were performed to verify the association of clinical and genetic variables with external apical root resorption (P <0.05). RESULTS: There was a higher proportion of external apical root resorption in orthodontically treated patients compared with the untreated subjects. In patients orthodontically treated, age higher than 14 years old, initial size of the maxillary incisor root superior to 30 mm, and premolar extraction were associated with increased external apical root resorption. Genotypes containing the C allele were weakly associated with protection against external apical root resorption (CC + CT × TT [odds ratio, 0.29; 95% confidence interval, 0.07-1.23; P = 0.091]) when treated orthodontic patients were compared to untreated individuals. CONCLUSIONS: Clinical factors and vitamin D receptor TaqI polymorphism were associated with external apical root resorption in orthodontic patients.

Analysis of the association of IL1B(C-511T) polymorphism with dental implant loss and the clusterization phenomenon.

OBJECTIVES: Endosteous dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host immune-inflammatory response is influenced by genetic factors. Interleukin-1 (IL-1) is a key mediator of inflammatory processes and functional polymorphisms in IL1 gene could be candidate genetic risk factors to study susceptibility to implant failure. The objective of this study was to investigate the association between IL1B (C-511T) genetic polymorphism and dental implant loss in a Brazilian population and its influence in the clusterization phenomenon. MATERIAL AND METHODS: The sample composed of 277 unrelated, both gender, mean age 53.63 ± 11.14 years individuals, divided into test group - 92 subjects with implant loss, and control group - 185 subjects with no implant loss. Patients' socioeconomic profile and clinical variables were investigated. Genomic DNA from oral mucosa was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There was significant difference between the groups in medical treatment (P=0.040), edentulism (P=0.019), and mean number of placed implants (P=0.001). There was difference between groups with and without implant loss neither considering genotypes (P=0.279) nor alleles (P=0.168) for IL1B (C-511T) polymorphism. When individuals showing up to one implant failure (n=254) were investigated vs. patients presenting multiple implant loss (n=23), no difference was either observed between groups for genotype (P=0.083) and allele (P=0.838) frequencies. CONCLUSIONS: The borderline association of the study polymorphism with implant loss suggests further IL1 haplotype analysis to elucidate the global involvement of IL-1 proteins in the modulation of the osseointegration process.

Exfoliative cytology of the oral mucosa in burning mouth syndrome: a cytomorphological and cytomorphometric analysis.

OBJECTIVE: The aim of this study was to evaluate oral epithelial cells by exfoliative cytology in burning mouth syndrome (BMS). MATERIAL AND METHODS: Oral smears were collected from clinically normal-appearing mucosa by liquid-based exfoliative cytology in 40 individuals (20 BMS patients and 20 healthy controls matched for age and gender) and analysed for cytological and cytomorphometric techniques. RESULTS: Mean values of nuclear area (NA) for experimental and control groups were, respectively, 67.52 and 55.64 µm² (p < 0.05). Cytoplasmic area (CA) showed the following mean values: 1258.0 (experimental) and 2069.0 µm² (control). Nucleus-to-cytoplasm area ratio for the experimental group was 0.07, besides the control group was 0.03 (p < 0.05). Morphologically, oral smears exhibited normal epithelial cells in both experimental and control groups. There was a significant predominance of nucleated cells of the superficial layer in the smears of BMS patients (p = 0.00001). CONCLUSION: This study revealed that oral mucosa of BMS patients exhibited significant cytomorphometric changes in the oral epithelial cells. These changes probably are associated with epithelial atrophy and a deregulated maturation process that may contribute to the oral symptoms of pain and discomfort in BMS.

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 Student's 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.

Proteomic Expression Profile in Human Temporomandibular Joint Dysfunction.

Temporomandibular joint dysfunction (TMD) is a multifactorial condition that impairs human's health and quality of life. Its etiology is still a challenge due to its complex development and the great number of different conditions it comprises. One of the most common forms of TMD is anterior disc displacement without reduction (DDWoR) and other TMDs with distinct origins are condylar hyperplasia (CH) and mandibular dislocation (MD). Thus, the aim of this study is to identify the protein expression profile of synovial fluid and the temporomandibular joint disc of patients diagnosed with DDWoR, CH and MD. Synovial fluid and a fraction of the temporomandibular joint disc were collected from nine patients diagnosed with DDWoR (n = 3), CH (n = 4) and MD (n = 2). Samples were subjected to label-free nLC-MS/MS for proteomic data extraction, and then bioinformatics analysis were conducted for protein identification and functional annotation. The three TMD conditions showed different protein expression profiles, and novel proteins were identified in both synovial fluid and disc sample. TMD is a complex condition and the identification of the proteins expressed in the three different types of TMD may contribute to a better comprehension of how each pathology develops and evolutes, benefitting the patient with a focus-target treatment.

Association of estrogen receptor alpha 1 and TMJ dysfunction: A pilot study.

OBJECTIVE: Temporomandibular disorder (TMD) is a multifactorial condition and the most common cause of orofacial pain, affecting mostly women, which points to a female hormone predilection. Therefore, the aim of this study was to analyze the association between TMD and estrogen receptor alpha 1 expression in disks of patients with TMD and condyle fracture (CFx). STUDY DESIGN: Forty specimens (from 27 patients) included n = 8 CFx, n = 21 anterior disk displacement with reduction (ADDwR), and n = 11 anterior disk displacement without reduction (ADDwoR). Age, area, and intensity of immunostaining were statistically compared between CFx, ADDwR, and ADDwoR groups using analysis of variance and Kruskal-Wallis analysis (P < .05). RESULTS: No significant difference between CFx, ADDwR, and ADDwoR groups with respect to age and expression of estrogen receptor alpha 1 was observed on immunohistochemical examination. CONCLUSION: No association of estrogen receptor alpha 1 expression and age was found in the CFx, ADDwR, and ADDwoR groups.

The role of polymorphism of the IL6 gene in tooth replantation.

The absence or presence of root resorption on the root surface of a replanted tooth indicates an immune-inflammatory reaction. Since interleukin-6 (IL-6) is considered an inflammatory marker in bone resorption, this study aimed to investigate the association between clinical variables and polymorphisms in IL6, with the outcome of replanted teeth at 1-year follow-up. Altogether, 127 avulsed teeth that were replanted and had their root canals treated were selected for this study. Periapical radiographs were taken after replantation and after 1 year. Real-time PCR was used to genotype IL6 polymorphisms. Chi-square and 'Z' tests were performed to verify the association between genetic variables and the prognosis of replanted teeth (P < 0.05). An association was observed between the rs2069843 polymorphism of IL6 and the outcome of replanted teeth (P < 0.05). The rs2069843 polymorphism of IL6 may influence the outcome of avulsed and replanted teeth in the first year post-trauma.

Lack of association between delayed tooth emergence and single nucleotide polymorphisms in estrogen receptors.

The purpose of the study was to investigate the association between single nucleotide polymorphisms (SNPs) in genes encoding estrogen receptors (ESR1 and ESR2, respectively) and delayed tooth emergence (DTE). This cross-sectional study was composed of biological unrelated children of both sexes, age ranging from 11 to 13 years old. DTE was defined when the successor primary tooth was still present in the oral cavity after its exfoliation time or the absence of the permanent tooth emergence into the oral cavity. Children were diagnosed with DTE when they had at least one delayed permanent tooth, according to age of exfoliation of each tooth proposed by The American Dental Association. Genomic DNA from saliva was used to evaluate the SNPs in ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938) using Real-Time PCR. Chi-square or Fisher exact tests and Logistic Regression adjusted by age and gender were performed. SNP-SNP interaction was accessed by multifactor dimensionality reduction (MDR) analysis also adjusted by gender and age. The established alpha of this study was 5%. Among 537 included children, 296 (55%) were in the "DTE" group and the 241 (45%) were in the "Control" group. Age and gender were not statistically different among the groups (p>0.05). Genotype distribution of the SNPs rs9340799, rs2234693, rs1256049 and rs4986938 were not associated with DTE (p> 0.05). The models elected by MDR were not statistically significant either. Conclusions: The studied SNPs in ESR1 and ESR2 were not associated with permanent DTE.

Calcium and Phosphorus Levels in Saliva are Influenced by Genetic Polymorphisms in Estrogen Receptor Alpha and Microrna17.

Homeostasis between salivary calcium and phosphorus is important for maintaining oral health. The aim of this study was to evaluate if polymorphisms in ESR1 (Estrogen Receptor Alpha), ESR2 (Estrogen Receptor Beta) and miRNA17 (microRNA17) are associated with calcium and phosphorus levels in saliva. Saliva from 276 12-year-old children were collected by masticatory stimulation and calcium and phosphorus levels were determined by Mass Spectrometry. Genomic DNA was extracted from remaining saliva and genetic polymorphisms in ESR1 (rs12154178, rs1884051, rs9340799 and rs2234693), in ESR2 (rs4986938 and rs1256049) and in miRNA17 (rs4284505) were genotyped using TaqMan chemistry and a real-time PCR equipment. Statistical differences in genotype and allele distributions between 'low' and 'high' calcium and phosphorus levels were determined using chi-square or Fisher´s exact tests. The analysis was also adjusted by sex (alpha of 5%). ESR1 rs9340799 had the less common genotype associated with higher calcium levels (p=0.03). The less common allele of ESR1 rs1884051 was associated with lower phosphorus levels (p=0.005) and there was an excess of heterozygotes for miRNA17 rs4284505 among individuals with lower calcium levels (p=0.002), both adjusted by sex. This study provides evidence that genetic polymorphisms in ESR1 and miRNA17 are involved in determining salivary calcium and phosphorus levels.

Strong and persistent microbial and inflammatory stimuli overcome the genetic predisposition to higher matrix metalloproteinase-1 (MMP-1) expression: a mechanistic explanation for the lack of association of MMP1-1607 single-nucleotide polymorphism genotypes with MMP-1 expression in chronic periodontitis lesions.

AIMS: Our objective was to evaluate the association between the MMP1-1607 single-nucleotide polymorphism (SNP), periodontopathogens and inflammatory cytokines with matrix metalloproteinase-1 (MMP-1) mRNA levels in vitro and in vivo. MATERIALS AND METHODS: This study investigated the influence of genetic (MMP1-1607 SNP), microbial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Actinobacillus actinomycetemcomitans) and inflammatory [tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)] factors on the determination of MMP-1 mRNA levels in periodontal tissues of non-smoker chronic periodontitis (CP, N=178) and control (C, N=190) groups. The effects of single and repeated lipopolysaccharide (LPS) and inflammatory cytokine stimulation of macrophages with distinct MMP1-1607 SNP genotypes were also investigated. RESULTS: In healthy tissues, the MMP1-1607 2G allele was associated with higher MMP-1 levels while in CP MMP-1 levels were associated with the presence and load of periodontopathogens, and also with TNF-alpha and IL-1beta expression irrespective of the MMP1-1607 genotype. In vitro data demonstrate that in 2G macrophages low- and intermediate-dose LPS and TNF-alpha+IL-1beta stimulation was associated with increased MMP-1 expression, while strong and repeated stimulation resulted in higher MMP-1 levels irrespective of the MMP1-1607 genotype. CONCLUSION: Our data demonstrate a limited role for MMP1-1607 SNP in periodontitis, where the extensive chronic antigenic challenge exposure overcomes the genetic control and plays a major role in the determination of MMP-1 expression.