RESUMEN

This study aimed to investigate the relationship between epigenetic mechanisms and oral mucositis (OM) in paediatric patients with acute lymphoblastic leukaemia. Oral cells were collected from 76 participants, including 15 healthy individuals, 10 patients with acute lymphoblastic leukaemia but without a history of OM and 51 acute lymphoblastic leukaemia patients with a history of OM (35 with active OM and 16 who had recovered from OM). Global DNA methylation in the miR-9-1 and miR-9-3 genes was performed. Seven polymorphisms rs1801131, rs1801133 (MTHFR), rs2228611 (DNMT1), rs7590760, rs1550117 (DNMT3A), rs6087990, rs2424913 (DNMT3B) were genotyped and an analysis of association with global DNA methylation was performed. The global methylation levels were lower in cancer patients recovered from OM than in the other groups. A higher frequency of unmethylated profile for miR-9-1 and partially methylated profile for miR-9-3 was observed in cancer patients regardless of OM history compared to healthy patients. The GG genotype of the rs2228611 (DNMT1) polymorphism was associated with higher levels of global methylation in cancer patients irrespective of OM. It was concluded that global methylation is associated with mucosal recovery. The effect of DNMT1 genotype on the global DNA methylation profile, as well as the methylation profile of miR-9-1 and miR-9-3 in cancer patients is independent of OM.

Asunto(s)

ADN (Citosina-5-)-Metiltransferasa 1 , Metilación de ADN , Epigénesis Genética , MicroARNs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Estomatitis , Humanos , Niño , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estomatitis/genética , Femenino , Masculino , MicroARNs/genética , ADN (Citosina-5-)-Metiltransferasa 1/genética , Preescolar , Genotipo , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A/genética , ADN Metiltransferasa 3B , Polimorfismo de Nucleótido Simple , Adolescente , Estudios de Casos y Controles , Metilenotetrahidrofolato Reductasa (NADPH2)

RESUMEN

The aim of this study was to investigate the DNA methylation profile in genes encoding catalase (CAT) and superoxide dismutase (SOD3) enzymes, which are involved in oxidative stress mechanisms, and in genes encoding pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-α) in the oral mucosa of oncopediatric patients treated with methotrexate (MTX®). This was a cross-sectional observational study and the population comprised healthy dental patients (n = 21) and those with hematological malignancies (n = 64) aged between 5 and 19 years. Oral conditions were evaluated using the Oral Assessment Guide and participants were divided into 4 groups: 1- healthy individuals; 2- oncopediatric patients without mucositis; 3- oncopediatric patients with mucositis; 4- oncopediatric patients who had recovered from mucositis. Methylation of DNA from oral mucosal cells was evaluated using the Methylation-Specific PCR technique (MSP). For CAT, the partially methylated profile was the most frequent and for SOD3 and IL6, the hypermethylated profile was the most frequent, with no differences between groups. For TNF-α, the hypomethylated profile was more frequent in the group of patients who had recovered from mucositis. It was concluded that the methylation profiles of CAT, SOD3, and IL6 are common profiles for oral cells of children and adolescents and have no association with oral mucositis or exposure to chemotherapy with MTX®. Hypomethylation of TNF-α is associated with oral mucosal recovery in oncopediatric patients who developed oral mucositis during chemotherapy.

Asunto(s)

Metotrexato , Mucosa Bucal , Estomatitis , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven , Antimetabolitos Antineoplásicos/efectos adversos , Estudios de Casos y Controles , Catalasa/genética , Estudios Transversales , Metilación de ADN , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/tratamiento farmacológico , Interleucina-6/genética , Interleucina-6/análisis , Metotrexato/uso terapéutico , Metotrexato/efectos adversos , Mucosa Bucal/efectos de los fármacos , Mucositis/genética , Mucositis/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/genética , Valores de Referencia , Estadísticas no Paramétricas , Estomatitis/genética , Estomatitis/inducido químicamente , Superóxido Dismutasa/genética , Factor de Necrosis Tumoral alfa/genética

RESUMEN

The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) and the DNA methylation profiles of the DNA methyltransferase (DNMT) gene family with oral mucositis in children and adolescents with hematologic malignancies treated with methotrexate (MTX®). The population was comprised of healthy and oncopediatric patients aged between 4 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, hematological, and biochemical data were obtained from medical records. Genomic DNA extracted from oral mucosal cells was used for the analysis of polymorphisms in DNMT1 (rs2228611), DNMT3A (rs7590760), and DNMT3B (rs6087990) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique (n = 102) and for DNA methylation using the methylation-specific PCR (MSP) technique (n = 85). The allele and genotypic frequencies of SNPs did not reveal any differences between patients with or without oral mucositis. An increase in the methylation frequency for DNMT1 in patients recovered from mucositis was detected. The DNMT3A methylated profile associated with the CC genotype (SNP rs7590760) appeared to be connected to higher values of creatinine. In addition, the DNMT3B unmethylated profile associated with the CC genotype (SNP rs6087990) appeared to be connected with higher values of creatinine. We conclude that the DNMT1 methylation profile is associated with the post-mucositis period and that the genetic and epigenetic profiles of DNMT3A and DNMT3B are associated with creatinine levels.

Asunto(s)

Mucositis , Estomatitis , Niño , Humanos , Adolescente , Preescolar , Adulto Joven , Adulto , Creatinina , Genotipo , Polimorfismo de Nucleótido Simple , Metilasas de Modificación del ADN , Estomatitis/genética

RESUMEN

OBJECTIVE: To investigate the relationship between the polymorphisms rs1544410 (BsmI), rs2228570 (FokI) and rs731236 (TaqI) and DNA methylation status in the VDR gene (vitamin D receptor) with oral mucositis (OM) in oncopaediatric patients treated with methotrexate (MTX®). METHODS: The population comprised healthy patients with haematological malignancies aged between 5 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, biochemical and haematological data were obtained from medical records. Genomic DNA from oral mucosal cells was used for the analysis of polymorphisms (n = 102) (PCR-restriction fragment length polymorphism) and DNA methylation (n = 81) (methylation-specific PCR). RESULTS: Males predominated (57.8%), and the mean age was 10.3 years (±4.7). OM affected 84.3% of patients, of which 53.1% developed severe oral mucositis (SOM). Patients with OM had lower platelet and leukocyte counts (p < 0.05). The G allele of rs1544410 (p = 0.040) and the CT genotype of rs2228570 polymorphisms were associated with SOM (p = 0.038). A partially methylated status in the VDR promoter was found in all patients. CONCLUSION: OM is associated with lower leukocyte and platelet counts. SOM is associated with the rs1544410 and rs2228570 polymorphisms. The methylation status of the VDR is not associated with inflammation or exposure to MTX®.

Asunto(s)

Predisposición Genética a la Enfermedad , Estomatitis , Masculino , Humanos , Niño , Preescolar , Adolescente , Adulto Joven , Adulto , Receptores de Calcitriol/genética , Polimorfismo de Nucleótido Simple , Estomatitis/genética , Metilación de ADN , Metotrexato

RESUMEN

OBJECTIVE: Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response. To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT -21 A/T), rs1800629 (tumor necrosis factor α, TNF- α -308 G/A), and rs1800795 (interleukin 6, IL-6 -174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients. METHODOLOGY: We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05. RESULTS: The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05). CONCLUSION: The AA genotype for CAT -21 A/T was a tendency among the group with severe OM. Data on TNF- α -308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 -174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis.

Asunto(s)

Estomatitis , Adolescente , Estudios Transversales , Femenino , Humanos , Masculino , Estrés Oxidativo/genética , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Estomatitis/inducido químicamente , Estomatitis/genética

RESUMEN

The aim of the present study was to analyze the relationship of OM with possible risk factors such as oral health condition, immunological status and IL-1ß profile in patients submitted to hematopoietic stem cell transplantation (HSCT). Fifty-four individuals submitted to HSCT were included. All patients received previous dental treatment and photobiomodulation (PBM) as the institutional OM preventive protocol. OM scores, immune status, and IL-1ß levels were determined during the conditioning period and at D+3 and D+8 after HSC infusion. IL-1ß gene polymorphism was also analyzed during conditioning. Possible associations of OM with risk factors were analyzed using conditional Fisher's exact test. OM was observed in 34 patients (62.9%) classified as Grade 1 (13 patients/24.1%), Grade 2 (14 patients/25.9%), Grade 3 (3 patients/5.5%), and Grade 4 (4 patients/7.4%). Allogeneic HSCT individuals exhibited a higher OM grade than autologous subjects. Moreover, an association was observed between severe OM and severe gingivitis (p = 0.01), neutropenia (p = 0.03), and leukopenia (p = 0.04). A significant association between OM and lower IL-1ß levels was detected at three time points, i.e., conditioning (p = 0.048), D+3 (p = 0.01), and D+8 (p = 0.005). The results showed that IL-1ß gene polymorphism was not associated with OM. Our study provided important insights into the scope of OM risk factors in the setting of HSCT. Patients submitted to HSCT with severe gingivitis prior to chemotherapy and with severe neutropenia and leukopenia exhibited a higher OM grade. Further investigation will be necessary to better understand the exact role of IL-1ß in the context of OM pathobiology and to validate cytokine analysis in larger cohorts.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Estomatitis , Estado de Salud , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Polimorfismo Genético , Factores de Riesgo , Estomatitis/genética , Acondicionamiento Pretrasplante

RESUMEN

The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

Asunto(s)

Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Estomatitis , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Adolescente , Niño , Femenino , Humanos , Recuento de Leucocitos , Estudios Longitudinales , Masculino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas de Neoplasias/genética , Polimorfismo Genético , Estomatitis/genética

RESUMEN

Abstract The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

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Resumo O presente estudo investigou a relação entre cinco polimorfismos genéticos e o desenvolvimento de mucosite oral em pacientes pediátricos recebendo quimioterapia com metrotexato. O estudo longitudinal foi conduzido com 64 pacientes e a mucosite oral avaliada pelo Oral Assessment Guide modificado, que tem como objetivo diagnosticar e classificar a mucosite oral. Células epiteliais bucais foram obtidas por bochecho e o DNA foi extraído. Os polimorfismos MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) e ABCG2 (rs2231142), foram analisados pela técnica de PCR-RFLP. Dados demográficos, hematológicos e bioquímicos foram coletados a partir de registros médicos. Análise estatística foi realizada utilizando o software SPSS adotando um valor de p=0,05. Observou-se que, o sexo masculino foi predominante (56,2%), e a idade média foi de 10,8 anos (± 4.9). A mucosite oral acometeu 65,6% dos pacientes, dos quais, 61,9% desenvolveram a forma grave da doença. Para o gene ABCG2 (rs2231142), o alelo raro A e o genótipo CA foram mais frequentes em indivíduos com mucosite (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). A gravidade da doença foi observada principalmente em pacientes mais jovens (mediana = 9 anos; p=0.02). Além disso, os pacientes com mucosite oral grave apresentaram menor contagem de leucócitos (mediana = 2150 mm3) em comparação aos pacientes com a forma leve/moderada (mediana = 4200 mm3; p=0.03). Pacientes do sexo feminino e aumento a cada 10.000 plaquetas foram fatores de proteção contra o aparecimento de mucosite oral (p=0.02). Concluiu-se que a presença do polimorfismo rs2231142 aumenta o risco de o paciente desenvolver a mucosite oral, bem como pacientes mais jovens e menor contagem de leucócitos contribui com a severidade.

Asunto(s)

Humanos , Masculino , Femenino , Niño , Adolescente , Estomatitis/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Polimorfismo Genético , Estudios Longitudinales , Recuento de Leucocitos , Proteínas de Neoplasias/genética

RESUMEN

Oral mucositis is an acute toxicity that occurs in patients submitted to chemoradiotherapy to treat head and neck squamous cell carcinoma. In this study, we evaluated differences in gene expression in the keratinocytes of the oral mucosa of patients treated with photobiomodulation therapy and tried to associate the molecular mechanisms with clinical findings. From June 2009 to December 2010, 27 patients were included in a randomized double-blind pilot study. Buccal smears from 13 patients were obtained at days 1 and 10 of chemoradiotherapy, and overall gene expression of samples from both dates were analyzed by complementary DNA (cDNA) microarray. In addition, samples from other 14 patients were also collected at D1 and D10 of chemoradiotherapy for subsequent validation of cDNA microarray findings by qPCR. The expression array analysis identified 105 upregulated and 60 downregulated genes in our post-treatment samples when compared with controls. Among the upregulated genes with the highest fold change, it was interesting to observe the presence of genes related to keratinocyte differentiation. Among downregulated genes were observed genes related to cytotoxicity and immune response. The results indicate that genes known to be induced during differentiation of human epidermal keratinocytes were upregulated while genes associated with cytotoxicity and immune response were downregulated in the laser group. These results support previous clinical findings indicating that the lower incidence of oral mucositis associated with photobiomodulation therapy might be correlated to the activation of genes involved in keratinocyte differentiation.

Asunto(s)

Quimioradioterapia , ADN Complementario/genética , Queratinocitos/metabolismo , Terapia por Luz de Baja Intensidad , Análisis por Micromatrices/métodos , Mucosa Bucal/efectos de la radiación , Método Doble Ciego , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estomatitis/etiología , Estomatitis/genética

RESUMEN

BACKGROUND AND OBJECTIVES: Increased expression of inflammatory cytokines in the oral cavity has been related to the etiopathogenesis of oral mucositis and to delayed oral mucosal repair. Low-level laser therapy (LLLT) stimulates proliferation and migration of gingival fibroblasts, but the effects of specific inflammatory cytokines on oral mucosal cells and the modulation of these effects by LLLT have not been fully investigated. Therefore, this study investigated the effects of LLLT on oral fibroblasts after being challenged by oral-mucositis-related inflammatory cytokines. METHODS: Human gingival fibroblasts were seeded in plain culture medium (DMEM) containing 10% fetal bovine serum (FBS) for 24 hours. Then, cells were kept in contact with inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8) in serum-free DMEM for 24 hours. After this period, cells were subjected to LLLT with a diode laser device (LaserTABLE, InGaAsP, 780 nm, 25 mW) delivering energy doses from 0.5 to 3 J/cm2 . Irradiation was repeated for 3 consecutive days. Twenty-four hours after the last irradiation, cell migration (wound-healing and transwell migration assays), cell proliferation (BrdU), gene expression of COL-I and growth factors (real-time PCR), and synthesis of COL-I (Sirius Red assay) and VEGF (ELISA) were assessed. Data were subjected to two-way ANOVA and Tukey's tests or Kruskall-Walis and Mann-Whitney tests (P < 0.05). RESULTS: The inflammatory cytokines decreased the migration capacity of gingival fibroblasts. However, a statistically significant difference was observed only for IL-6, detected by transwell assay, where 30% less cells migrated through the pores (P < 0.05) and IL-8, with an increased wound area (116%; P < 0.05), detected by the wound healing method. Cell proliferation was not affected by contact with cytokines, while growth factors and COL-I expression (approximately 80%; P < 0.05), as well as VEGF synthesis (approximately 20%; P < 0.05), were decreased after contact to all tested cytokines. The opposite was seen for total collagen synthesis. LLLT promoted an acceleration of fibroblast migration (30%; P < 0.05) and proliferation (112%; P < 0.05) when delivering 0.5 J/cm2 to the cells previously in contact with the inflammatory cytokines. Gene expression of VEGF (approximately 30%; P < 0.05), and EGF (17%; P < 0.05), was stimulated by LLLT after contact with TNF-α and IL-6. CONCLUSION: LLLT can counteract the negative effects of high concentrations of inflammatory cytokines, especially IL-6 and IL-8 on gingival fibroblast functions directly related to the wound-healing process. Lasers Surg. Med. 48:1006-1014, 2016. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Citocinas/metabolismo , Fibroblastos/efectos de la radiación , Láseres de Semiconductores/uso terapéutico , Terapia por Luz de Baja Intensidad/métodos , Mucosa Bucal/efectos de la radiación , Estomatitis/radioterapia , Cicatrización de Heridas/efectos de la radiación , Adulto , Biomarcadores/metabolismo , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Fibroblastos/fisiología , Regulación de la Expresión Génica/efectos de la radiación , Encía/fisiología , Encía/efectos de la radiación , Humanos , Mucosa Bucal/fisiología , Estomatitis/genética , Estomatitis/metabolismo , Cicatrización de Heridas/fisiología

RESUMEN

INTRODUCTION: Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side-effect of cancer therapy. AIM: To evaluate the effect of the topical application of S-nitrosoglutathione (GSNO), a nitric oxide donor, on 5-fluorouracil (5-FU)-induced oral mucositis in hamsters. MATERIALS AND METHODS: Oral mucositis was induced in male hamsters by two intraperitoneal administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day. Animals received saline, HPMC or HPMC/GSNO (0.1, 0.5 or 2.0 mM) 1 h prior to the 5-FU injection and twice a day for 10 or 14 days. Samples of cheek pouches were harvested for: histopathological analysis, TNF-α and IL-1ß levels, immunohistochemical staining for iNOS, TNF-α, IL-1ß, Ki67 and TGF-ß RII and a TUNEL assay. The presence and levels of 39 bacterial taxa were analyzed using the Checkerboard DNA-DNA hybridization method. The profiles of NO released from the HPMC/GSNO formulations were characterized using chemiluminescence. RESULTS: The HPMC/GSNO formulations were found to provide sustained release of NO for more than 4 h at concentration-dependent rates of 14 to 80 nmol/mL/h. Treatment with HPMC/GSNO (0.5 mM) significantly reduced mucosal damage, inflammatory alterations and cell death associated with 5-FU-induced oral mucositis on day 14 but not on day 10. HPMC/GSNO administration also reversed the inhibitory effect of 5-FU on cell proliferation on day 14. In addition, we observed that the chemotherapy significantly increased the levels and/or prevalence of several bacterial species. CONCLUSION: Topical HPMC/GSNO accelerates mucosal recovery, reduces inflammatory parameters, speeds up re-epithelization and decreases levels of periodontopathic species in mucosal ulcers.

Asunto(s)

Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , S-Nitrosoglutatión/administración & dosificación , Estomatitis/tratamiento farmacológico , Administración Tópica , Animales , Cricetinae , Modelos Animales de Enfermedad , Fluorouracilo/efectos adversos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/genética , Inflamación/patología , Interleucina-1beta/biosíntesis , Masculino , Neoplasias/patología , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Estomatitis/inducido químicamente , Estomatitis/genética , Estomatitis/patología , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis

RESUMEN

PURPOSE: To investigate the association between interleukin-6 (IL-6) G174C polymorphism and susceptibility to peri-implant disease (PID) and/or chronic periodontitis (CP), in Brazilian subjects. MATERIALS AND METHODS: A total of 103 Brazilian patients were submitted to peri-implant and periodontal examination. According to their peri-implant characteristics, patients were divided into: group A (healthy, n = 52), group B (peri-implant mucositis, n = 20), and group C (peri-implantitis, n = 31). All patients (n = 103) were also characterized as healthy periodontium patients without CP (HP, n = 60) or CP patients (CP, n = 43). DNA was extracted from buccal cells, and the IL-6 G174C polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Differences in the prevalence of genotypes and alleles between healthy and ill patients were analyzed by chi-square test (P < .05), considering PID, CP, and PID+CP. RESULTS: Results considered the presence of PID and/or CP in all patients. The CC genotype was the least common in all groups. The chi-square test showed no significant correlation between genotypes. However, the odds ratio showed that individuals with GG genotype and allele G were 1.53 and 1.43 times more susceptible to PID, respectively. The risk of presenting CP was increased in patients with GG genotype and allele G 1.35 and 1.24 times, respectively. When both diseases were evaluated together, patients with GG genotypes and allele G were 1.75 and 1.50 times more likely to present PID and CP together. When PID was evaluated without CP, patients with allele G were 2.08 times more susceptible to PID. CONCLUSIONS: The frequency of the genotype IL-6 174GG and allele G was different between healthy and ill groups. Therefore, this genotype may be a common risk factor for both CP and PID in Brazilian populations.

Asunto(s)

Periodontitis Crónica/genética , Predisposición Genética a la Enfermedad/genética , Interleucina-6/genética , Periimplantitis/genética , Polimorfismo Genético/genética , Adulto , Alelos , Brasil , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Estomatitis/genética