RESUMEN

BACKGROUND: The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C-rs1042522; p53 PIN3-rs17878362; p21 31 C > A-rs1801270; p21 70 C > T-rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population. METHODS: Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis. RESULTS: Protective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively). CONCLUSIONS: Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients.

Asunto(s)

Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Lupus Eritematoso Sistémico , Proteína p53 Supresora de Tumor , Femenino , Humanos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Lupus Eritematoso Sistémico/genética , Polimorfismo Genético , Serositis , Proteína p53 Supresora de Tumor/genética

RESUMEN

Abstract Background The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C—rs1042522; p53 PIN3—rs17878362; p21 31 C > A—rs1801270; p21 70 C > T—rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population. Methods Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis. Results Protective effect was observed for the genotype combinations p53 PIN3 A1/A1 -p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively). Conclusions Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients. Highlights The polymorphisms TP53 rs1042522 (G > C) and TP53 rs17878362 (16 bp Del/Ins) were associated with SLE risk in whites. In whites, the combined genotype TP53 rs1042522 GC- TP53 rs17878362 A1A2 and the haplotype TP53 rs1042522 C-rs17878362 A2 represented higher SLE risk. Combination of TP53 rs17878362 (16 bp Del/Ins) and p21 rs1801270 (C > A) protected against SLE in non-white women. TP53 and p21 (CDKN1A) polymorphisms may be SLE susceptibility markers for specific groups.

RESUMEN

Patients with systemic lupus erythematosus have a higher incidence of neoplasms associated with human papillomavirus infections, such as those that affect the vulva, the vagina, and the cervix; however, little is known about the frequency of anal cancer among these patients. Although there are recommendations for screening for this cancer in immunosuppressed individuals, it is possible that this procedure is not strictly followed. We describe the case of a 47-year-old woman with systemic lupus erythematosus who was treated with immunosuppressants and developed advanced anal squamous cell carcinoma after adequate treatment and healing of a high-grade cervical squamous intraepithelial lesion. Five years after the completion of the anal cancer treatment, the patient presented with cystic hepatic lesions that were histopathologically confirmed to be metastatic squamous cell carcinoma. This report aimed to highlight the need for anal cancer screening in patients with lupus, particularly if there was a history of cervical cytopathological alterations. (AU)

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Resumo Pacientes com lúpus eritematoso sistêmico apresentam maior incidência de neoplasias associadas a infecções por HPV, como aquelas que acometem a vulva, a vagina e o colo do útero, mas pouco se sabe sobre a frequência de câncer anal entre essas pacientes. Embora existam recomendações para o rastreamento desse câncer em indivíduos imunossuprimidos, é possível que esse procedimento não esteja sendo rigorosamente seguido. Descrevemos uma mulher de 47 anos com lúpus eritematoso sistêmico, tratada com imunossupressores, que desenvolveu um carcinoma escamocelular anal avançado após tratamento adequado e cicatrização de lesão intraepitelial escamosa cervical de alto grau. Cinco anos após o término do tratamento do câncer anal, a paciente apresentou lesões císticas hepáticas cujo resultado citopatológico confirmou ser carcinoma escamocelular metastático. O presente relato teve como objetivo chamar atenção para a necessidade do rastreamento do câncer anal em pacientes com lúpus, principalmente se houver história prévia de alterações citopatológicas cervicais. (AU)

Asunto(s)

Humanos , Femenino , Persona de Mediana Edad , Neoplasias del Ano/diagnóstico , Carcinoma Adenoescamoso , Lupus Eritematoso Sistémico , Infecciones por Papillomavirus , Neoplasias Hepáticas/secundario

RESUMEN

Introduction: the prevalence of cervical and anal human papillomavirus (HPV) infection in women infected with human immunodeficiency virus (HIV) is high. However, little is known about the differences in the susceptibility of these infections and related lesions. The aim of this study was to describe the association between the prevalence of cervical and anal HPV infection and HPV-related lesions in HIV-positive women. Methods: this study included 88 HIV-positive women attending an outpatient clinic in a university hospital. Ectocervical, endocervical, and anal samples were collected for colpocytology and anal cytology. A polymerase chain reaction-based technique was used to detect HPV deoxyribonucleic acid in endocervical and anal swab samples. Results: the cervical and anal HPV positivity rates were 35.21% and 78.8%, respectively. The presence of HPV-related lesions on colpocytology was associated with anal HPV positivity (P = 0.027). The ratio between cervical HPV infection and cervical HPV-related lesions was 2.5. The ratio between anal HPV infection and anal HPV-related lesions was 4.3. Overall, 30% had concomitant HPV DNA in the cervix and anus. Conclusion: there are differences in the susceptibility of infections and related lesions between the cervix and anus. Despite a higher incidence of anal HPV, the progression to HPV-related lesion does not occur via the same manner in the cervix and anus. Moreover, cervical HPV-related lesions in HIV-positive women may serve as a cue for anal preventive strategies, and further investigations in these women may be useful.

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Introdução: as infecções cervicais e anais pelo papilomavírus humano (HPV) em mulheres infectadas com o vírus da imunodeficiência umana (HIV) são muito prevalentes. Entretanto, pouco se sabe sobre as diferenças na suscetibilidade entre essas infecções e as lesões HPV-relacionadas. Objetivo: descrever a associação entre as prevalências de infecção cervical e anal pelo HPV e lesões relacionadas em mulheres HIV-positivas. Metodologia: este estudo incluiu 88 mulheres HIV-positivas atendidas em ambulatório de hospital universitário. Amostras ectocervicais, endocervicais e anais foram coletadas para colpocitologia e citologia anal. Uma técnica baseada na reação em cadeia da polimerase foi usada para detectar o ácido desoxirribonucléico (DNA) do HPV em amostras de swabs endocervical e anal. Resultado: as taxas de positividade do HPV cervical e anal foram de 35,21% e 78,8%, respectivamente. As lesões relacionadas ao HPV na colpocitologia foram associadas à positividade anal para o HPV (P = 0,027). A proporção entre infecção cervical por HPV e lesões cervicais relacionadas foi de 2,5. A proporção entre a infecção anal por HPV e as lesões anais relacionadas foi de 4,3. 30% tinham DNA-HPV concomitante no colo do útero e ânus. Conclusão: existem diferenças na suscetibilidade de infecções e de lesões relacionadas entre o colo e o ânus. Apesar de maior incidência de HPV anal, a progressão para lesões relacionadas não ocorre da mesma forma no colo e no ânus. Além disso, lesões cervicais relacionadas ao HPV em mulheres HIV positivas podem servir como pista para estratégias preventivas anais. Investigações adicionais podem ser úteis.

Asunto(s)

Humanos , Femenino , Neoplasias del Ano , VIH , Alphapapillomavirus , Estudios Transversales

RESUMEN

OBJECTIVE: The aim of this study was to investigate the presence of human papillomavirus (HPV) in biopsy specimens from juvenile and adult patients with histopathological diagnosis of recurrent respiratory papillomatosis (RRP) treated in two public hospitals in Rio de Janeiro, Brazil. METHODS: We performed the detection and genotyping of HPV by PCR technique for the types 6, 11, 16, and 18 in biopsy specimens from 41 RRP patients. RESULTS: The juvenile onset RRP (JoRRP) corresponded to 61% and the adult onset RRP (AoRRP) corresponded to 39% of the study group. Prevalence of males was observed in both the adult (81.3%) and the juvenile (56%) groups. Lesions in the larynx were more frequent in the glottis (46%). Genotyping analysis only revealed patients with HPV-6 (34.1%), HPV-11(17.1%), and co-infection HPV-6 and -11 (48.8%). RRP severity was significantly associated with the JoRRP (p<0.001), with extralaryngeal disease and more surgeries. However, no significant association between RRP severity and HPV types was found. One co-infected patient in the JoRRP died due to the evolution of the disease with lung involvement. CONCLUSION: These results show the strong association of HPV-6 and/or HPV-11 types with RRP and could complement the diagnosis, prognosis, and therapies for these patients. In addition, the HPV vaccination should be encouraged to prevent the disease.

Asunto(s)

Enfermedades de la Laringe/epidemiología , Enfermedades Pulmonares/epidemiología , Infecciones por Papillomavirus/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Enfermedades de la Tráquea/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Femenino , Genotipo , Papillomavirus Humano 11/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Papillomavirus Humano 6/genética , Humanos , Enfermedades de la Laringe/virología , Enfermedades Pulmonares/virología , Masculino , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Prevalencia , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Riesgo , Enfermedades de la Tráquea/virología

RESUMEN

OBJECTIVE: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. METHODS: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n=91) and controls (n=97). RESULTS AND CONCLUSIONS: The 857GA genotype was more prevalent among nonwhite SLE patients (OR=4.01, 95% CI=1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR=1.97; 95% CI=1.01-3.81).

Asunto(s)

Arilamina N-Acetiltransferasa/genética , Lupus Eritematoso Sistémico/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos

RESUMEN

ABSTRACT Objective: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. Methods: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n = 91) and controls (n = 97). Results and conclusions: The 857GA genotype was more prevalent among nonwhite SLE patients (OR = 4.01, 95% CI = 1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR = 1.97; 95% CI = 1.01-3.81).

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RESUMO Objetivo: Investigar potenciais associações de quatro substituições do gene NAT2 (N-acetiltransferase 2) e do fenótipo acetilador de NAT2 com o lúpus eritematoso sistêmico (LES) e os fenótipos clínicos. Métodos: A análise molecular das substituições 481C > T, 590G > A, 857G > A e 191G > A do gene NAT2 foi feita com a técnica de PCR-RFLP, usando DNA extraído de amostras de sangue periférico obtidas de pacientes com LES (n = 91) e controles (n = 97). Resultados e conclusões: O genótipo 857GA foi mais prevalente entre pacientes com LES não brancas (OR = 4,01, IC 95% = 1,18-13,59). O alelo 481 T apresentou associação positiva com as alterações hematológicas que envolvem mecanismos autoimunes, especificamente anemia hemolítica autoimune ou trombocitopenia autoimune (OR = 1,97; IC 95% = 1,01-3,81).

Asunto(s)

Humanos , Arilamina N-Acetiltransferasa/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Lupus Eritematoso Sistémico/genética , Predisposición Genética a la Enfermedad/genética , Genotipo

RESUMEN

BACKGROUND: Although the interleukin-1 (IL-1) plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. AIMS: To investigate the importance of IL1B-511C>T (rs16944), IL1B +3954C>T (rs1143634), and IL1RN intron 2 variable number tandem repeat (VNTR) (rs2234663) polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. SUBJECTS AND METHODS: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43) and chronic (chronic periodontitis [CP], n = 52) periodontitis, and controls (n = 50) were genotyped by polymerase chain reaction (PCR) (IL1RN intron 2 VNTR) or PCR-restriction fragment length polymorphism (PCR-RFLP) (IL1B-511 C>T and IL1B + 3954C>T) techniques. STATISTICAL ANALYSIS: The independent t-test, Chi-square, and Fisher's exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. RESULTS: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84), particularly in smokers (OR = 4.43) and females (OR = 6.00). The minor alleles IL1RN*2 and *3 increased the risk of AgP (OR = 2.18), especially the IL1RN*2*2 genotype among  white Brazilians (OR = 7.80). Individuals with the combinations of the IL1B + 3954T and IL1RN*2 or *3-containing genotypes were at increased risk of developing CP (OR = 4.50). Considering the three polymorphisms (rs16944, rs1143634, and rs2234663), the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41) and CP (OR = 6.39), respectively. CONCLUSIONS: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals.

RESUMEN

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions.

Asunto(s)

Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Estudios de Casos y Controles , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/fisiología , Etnicidad/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias/fisiología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Lesiones Intraepiteliales Escamosas de Cuello Uterino/epidemiología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología

RESUMEN

We investigated the importance of two adjacent functional polymorphisms in the Murine Double Minute 2 (MDM2) gene, SNP285 G > C and SNP309 T > G, for the development of cervical lesions in a Southeastern Brazilian population (293 cases and 184 controls). MDM2 genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and/or DNA sequencing. MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut (>16 years). Besides, this polymorphism may help identify women at risk of developing severe cervical lesion at a young age (<30 years).

Asunto(s)

Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-mdm2/genética , Neoplasias del Cuello Uterino/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Etnicidad , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Neoplasias del Cuello Uterino/epidemiología , Adulto Joven

RESUMEN

Variants of p16(INK4a) and p14(ARF), encoded by the CDKN2A locus, may respond differently to the presence of human papillomavirus (HPV). We investigated the potential association of two CDKN2A polymorphisms, 500C > G (rs11515) and 540C > T (rs3088440), with cervical neoplasia in patients with cervical lesions and healthy controls (n = 492). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and/or DNA sequencing techniques were employed for genotyping. The 500G allele was found higher, whereas the 540T/T genotype was less frequent in patients with more severe lesions. The CDKN2A variants may have the potential to be markers for the management of patients with cervical neoplasia.

Asunto(s)

Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Polimorfismo de Nucleótido Simple , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADN , Índice de Severidad de la Enfermedad , Neoplasias del Cuello Uterino/patología , Adulto Joven , Displasia del Cuello del Útero/patología

RESUMEN

A doença periodontal é uma doença crônica multifatorial que afeta os tecidos de suporte do dente. Seu início é decorrente da ação de micro-organismos do biofilme dentário, resultando em uma resposta imunoinflamatória do hospedeiro que poderia causar um dano tecidual. Diversas citocinas anti-inflamatórias são produzidas por diferentes tipos celulares durante o processo patogênico da doença periodontal visando limitar essa resposta. Dentre elas, destaca-se a interleucina-10 (IL-10), que possui funções relacionadas à inibição da fagocitose de células inflamatórias. Dessa forma, este trabalho teve por objetivo revisar a literatura acerca da importância da IL-10 para a patogênese da doença periodontal.

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Periodontal disease is a multifactorial chronic disease that affects the supportive tissues of tooth. This process initiates through the action of microorganisms of dental biofilm, which results in a host immunoinflammatory response that could cause tissue damage. Different anti-inflammatory cytokines are produced by several cell types during the pathogenic process of periodontal disease in order to reduce the inflammatory response. This group of molecules includes the interleukin 10 (IL-10), whose functions are related to phagocytosis inhibition of inflammatory cells. Taking all this into consideration, the aim of this work was to review the literature about the importance of IL-10 for the pathogenesis of periodontal disease.

Asunto(s)

Periodoncia , Periodontitis

RESUMEN

Indivíduos com doença inflamatória intestinal (DII) apresentam uma maior prevalência de periodontite. O objetivo desse estudo piloto foi investigar a presença do polimorfismo do gene do TNF-A -308 G>A em indivíduos com DII e periodontite comparando com indivíduos sistemicamente saudáveis com periodontite. Nossa hipótese é que nos indivíduos com DII e periodontite, a presença do polimorfismo do fator de necrose tumoral (TNFA) -308 G>A seja mais prevalente. Dez pacientes com Doença de Crohn (DC) e periodontite, 6 pacientes com retocolite ulcerativa idiopática (RCUI) e periodontite e 8 pacientes sem DII com periodontite participaram desse estudo. Foram considerados com periodontite indivíduos com perda de inserção clínica maior ou igual a 3 mm em pelo menos 4 sítios em diferentes dentes. Células epiteliais da mucosa oral foram coletadas com cotonetes esterilizados. O DNA foi extraído através de um kit comercial. O DNA obtido foi utilizado como molde em reações de amplificação das regiões genômicas de interesse através da técnica de reação em cadeia polimerase - PCR, utilizando-se oligonucleotídeos específicos. A comparação entre grupos foi feita com o teste ANOVA e com o teste T. O teste x² foi utilizado para analisar a presença do polimorfismo. O nível de significância foi determinado em 5% (p< 0,05). Nos pacientes com DC, 60% apresentavam 1 alelo polimórfico. Nos com RCUI, não foi encontrado o alelo polimórfico. Nos saudáveis com periodontite, 25% apresentaram o alelo polimórfico. Esse estudo demonstrou que pacientes com DC e periodontite possuíam uma maior prevalência de um alelo polimórfico do TNFA -308 G> A. Esse resultado sugere que apesar de não necessariamente determinar a ocorrência da DII e nem da periodontite, o polimorfismo do TNFA -308 G>A pode exercer um papel na modificação do fenótipo de pacientes com DII e periodontite

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Subjects with inflammatory bowel disease (IBD) have a higher prevalence of peridontitis. The aim of this pilot study was to assess the polymorphism of TNFA -308 G>A in IBD patients who had periodontitis and to compare to systemically health individuals who have periodontitis. Our hypothesis is that in subjects with IBD and periodontitis the occurrence of a genetic polymorphism of tumor necrosis factor alpha (TNFA) -308 G>Ais more prevalent. Ten patients with Crohn 's Disease (CD), 6 patients with ulcerative colitis (UC) and 8individuals systemically health otherwise periodontitis were included in this study. Periodontitis was defined by clinical attachment loss equal or higher 3 mm in at least 4 sites in different teeth. Epithelial cells from the oral mucosa were obtained through a sterilized swab. The DNA extraction was realized through a commercial kit. The obtained DNA was used for the aimed region in polymerase chain reaction –PCR using specific oligonucleotides. Comparisons between the groups were analyzed by ANOVA and T tests. To analyze thepresence of the polymorphism x² test was used. Significance was set at 5% (p< 0.05). Sixty per cent of CD patients had one polymorphicalele. None of UC patients had the polymorphic allele. Twenty five per cent of systemically health individuals had the polymorphic allele. This study showed that patientswith Crohn 's Disease who have periodontitis present a higher prevalance of the polymorphic allele of TNA-308. This preliminary result suggests that although this polymorphism is not a risk for occurrence of IBD or periodontitis, this polymorphism may have a role in modifying the phenotype of IBD patients who have periodontitis.

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Periodontitis

RESUMEN

Oesophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and is the sixth cause of cancer-related death in the world. Inactivation of cell-cycle regulating genes, such as p14ARF and p16INK4a, and cell adhesion genes, such as E-cadherin, is common in cancer, and results from genetic and/or epigenetic alterations. Therefore, we have analysed the mRNA expression of p14ARF, p16INK4a and E-cadherin in 17 matched ESCC and normal mucosal samples obtained from Brazilian patients by semi-quantitative RT-PCR. The expression of p14ARF and p16INK4a was absent or reduced in several ESCC samples. Hypermethylation of CpG islands, caused by the action of DNA methyltransferases (DNMTs), is a major form of epigenetic inactivation of the p14ARF and p16INK4a genes in tumours. Hence, we also investigated the mRNA expression of the human DNA methyltransferases in normal oesophageal mucosa and in the tumour matched samples. All DNMTs were constitutively expressed in the normal oesophageal mucosa but a significantly higher expression of DNMT3B was observed in the tumours. Data analysis by the Spearman rank test showed that the expression of DNMT3B was inversely correlated with that of p14ARF and p16INK4a. Our results suggest that DNMT3B over-expression may be involved in the suppression or lower expression of p14ARF and p16INK4a observed in ESCC.

Asunto(s)

Carcinoma de Células Escamosas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteína p14ARF Supresora de Tumor/metabolismo , Anciano , Cadherinas/genética , Cadherinas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Regulación hacia Abajo , Esófago/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Análisis por Apareamiento , Metilación , Persona de Mediana Edad , Membrana Mucosa/metabolismo , ARN Mensajero/análisis , Estadísticas no Paramétricas , Células Tumorales Cultivadas , Proteína p14ARF Supresora de Tumor/genética , ADN Metiltransferasa 3B

RESUMEN

Vários estudos em genética humana têm utilizado a tecnologia do chip com múltiplos marcadores para a genotipagem de polimorfismos de único nucleotídeo (SNPs). Paralelamente, um número crescente de estudos busca a base molecular da predisposição à periondontite através dos polimorfismos. Os objetivos do presente estudo foram: testar um método alternativo de coleta de células de indivíduos com periodontite agressiva para a obtenção do DNA genômico; avaliar a qualidade do DNA extraído; testar sua utilização para genotipagem dos SNPs através da tecnologia do chip (Affymetrix GeneChip®10K, Santa Clara, CA). O método alternativo de coleta de células, além de menos invasivo mostrou-se adequado aos objetivos propostos.

Asunto(s)

Humanos , ADN , Genotipo , Periodontitis/genética , Polimorfismo de Nucleótido Simple/genética