1. Universidade Federal da Bahia
  2. Instituto de Ciências da Saúde (ICS)
  3. Programa de Pós-Graduação em Processos Interativos dos Órgãos e Sistemas (PPGPIOS)
  4. Dissertação (PPGPIOS)
Use este identificador para citar ou linkar para este item: https://repositorio.ufba.br/handle/ri/34744
Tipo: Dissertação
Título: Influence of genetic variants on RANK, RANKL and OPG genes in periodontitis.
Título(s) alternativo(s): Influência de variantes genéticas nos genes RANK, RANKL e OPG na periodontite.
Autor(es): Oliveira, Francine Vilma de
Primeiro Orientador: Carletto, Tatiane de Oliveira Teixeira Muniz
metadata.dc.contributor.advisor-co1: Figueiredo, Camila Alexandrina
metadata.dc.contributor.referee1: Carneiro, Valdirene Leão
metadata.dc.contributor.referee2: Carletto, Tatiane de Oliveira Teixeira Muniz
metadata.dc.contributor.referee3: Figueiredo, Camila Alexandrina
metadata.dc.contributor.referee5: Martins, Gabriela Botelho
Resumo: Introdução: A periodontite é uma doença inflamatória multifatorial que afeta os tecidos de suporte do dente, podendo levar à perda dental. A interação de complexos bacterianos específicos envolvidos na periodontite, fatores de risco que interferem na resposta imunológica do hospedeiro, incluindo, por exemplo, a regulação celular de fibroblastos, osteoblastos e osteoclastos, e a suscetibilidade genética e variantes específicas, podem estar associados à doença e à dificuldade do tratamento. O sistema RANKL/RANK/OPG está envolvido na diferenciação e ativação dos osteoclastos, regulando as respostas celulares e a reabsorção óssea na periodontite. Variantes genéticas podem influenciar na manifestação desses genes, que têm sido associados a doenças, em diferentes populações. Objetivos: Descrever a frequência e o potencial regulatório das variantes do sistema RANK, RANKL e OPG; avaliar o seu potencial como marcadores genéticos informativos de ancestralidade (AIM); avaliar a associação de variantes genéticas em RANK, RANKL e OPG com a presença de periodontite. Metodologia: Estudo transversal com 506 indivíduos adultos participantes de uma coorte, acometidos de asma e periodontite. Estes tiveram o DNA genômico extraído e genotipado, utilizando-se a plataforma Illumina Multi-Ethnic Global Array (MEGA, Illumina). As plataformas NCBI, Regulome DB, Haploview 4.2 e rSNPBase foram consultadas e utilizadas. Para as análises de associação, foram classificados com presença (n=117) ou ausência (n=389) de periodontite; e a análise estatística foi realizada com o software PLINK 1.9, mediante regressão logística ajustada por idade, obesidade, hábito de respirar pela boca, uso de fio dental, asma e componente principal de ancestralidade. Resultados: As variantes mais frequentes na população estudada foram: o rs4941129 em RANK, frequência de menor alelo (MAF) 50%; o rs9525641 em RANKL, MAF 46% e o rs3102724 em OPG, MAF 46%. Os rs 17069898 (1f) em RANK, rs2200287 (1d) em RANKL e rs3134063 (1f) em OPG apresentaram maior impacto funcional. Em OPG e RANK, nove polimorfismos se caracterizaram como AIM, predominando populações YRI (africanos) e CEU (europeus). Foram associados à periodontite no gene RANK, 27 SNV (variante de nucleotídeo único), sendo 20 positivamente (odds ratio >1) e 16 deles apresentam alta correlação entre si, variando entre 81% e 100%; e 7 negativamente (odds ratio<1) e 2 deles com alta correlação (96%), enquanto 2 em perfeito equilíbrio (r2=1,0). Em RANKL, 11 SNV foram associados positivamente à periodontite, sendo que 6 estão em perfeito equilíbrio (r2=1,0) e 4 em alta correlação, variando de 96% a 100%. Em OPG, 2 SNV foram associados positivamente à periodontite. Essas variantes estão em alto desequilíbrio de ligação (r2=0.99). Foi demonstrado, no gene RANK, 1f (rs4941125), 2b (rs55850220) e 3a (rs34432351, rs72931591 e no gene RANKL 3a (rs115675044 e rs443188), que há possibilidade de envolvimento em regiões reguladoras e funcionais. Conclusão: Variantes nos RANK, RANKL e OPG se mostraram frequentes na população estudada e tiveram seus alelos mais frequentes associados a doenças em populações ancestrais; e 40 variantes delas estão associadas e positiva e negativamente à periodontite.
Abstract: Introduction: Periodontitis is a multifactorial inflammatory disease that affects the supporting tissues of the tooth, which can lead to tooth loss. The interaction of specific bacterial complexes involved in periodontitis, risk factors that interfere with the immune response of the host, including, for example, the cellular regulation of fibroblasts, osteoblasts and osteoclasts, and genetic susceptibility and specific variants, may be associated with the disease and to the difficulty of treatment. The RANKL/RANK/OPG system is involved in osteoclast differentiation and activation, regulating cellular responses and bone resorption in periodontitis. Genetic variants can influence the expression of these genes, which have been associated with diseases, in different populations. Objectives: Describe the frequency and regulatory potential of RANK, RANKL and OPG system variants; assess their potential as ancestry informative genetic markers (AIM); to evaluate the association of genetic variants in RANK, RANKL and OPG with the presence of periodontitis. Methodology: Cross-sectional study with 506 adult individuals participating in a cohort, affected by asthma and periodontitis. The genomic DNA was extracted and genotyped using the Illumina Multi-Ethnic Global Array (MEGA, Illumina) platform. The NCBI, Regulome DB, Haploview 4.2 and rSNPBase platforms were consulted and used. For association analyses, they were classified as having the presence (n=117) or absence (n=389) of periodontitis; and statistical analysis was performed using the PLINK 1.9 software, using logistic regression adjusted for age, obesity, mouth breathing habit, flossing, asthma and main component of ancestry. Results: The most frequent variants in the population studied were: rs4941129 in RANK, lowest allele frequency (MAF) 50%; the rs9525641 in RANKL, MAF 46% and the rs3102724 in OPG, MAF 46%. The rs 17069898 (1f) in RANK, rs2200287 (1d) in RANKL and rs3134063 (1f) in OPG had greater functional impact. In OPG and RANK, nine polymorphisms were characterized as AIM, predominantly YRI (African) and CEU (European) populations. They were associated with periodontitis in the RANK 27 SNV gene (single nucleotide variant), 20 of which were positively (odds ratio >1) and 16 of them showed high correlation with each other, ranging from 81% to 100%; and 7 negatively (odds ratio<1) and 2 of them with high correlation (96%), while 2 in perfect balance (r2=1.0). In RANKL, 11 SNV were positively associated with periodontitis, with 6 being in perfect balance (r2=1.0) and 4 in high correlation, ranging from 96% to 100%. In OPG, 2 SNV were positively associated with periodontitis. These variants are in high linkage disequilibrium (r2=0.99). In the RANK gene 1f (rs4941125), 2b (rs55850220) and 3a (rs34432351, rs72931591 and in the RANKL 3a gene (rs115675044 and rs443188) there is a possibility of involvement in regulatory and functional regions. Conclusion: Variants of the RANK, RANKL and OPG genes were frequent in the population studied and had their most frequent alleles associated with diseases in ancestral populations; and 40 variants are positively and negatively associated with periodontitis.
Palavras-chave: Variante de único nucleotídeo
RANK
RANKL
OPG
Periodontite
Single Nucleotide Variant
Periodontitis
CNPq: CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA::PERIODONTIA
Idioma: por
País: Brasil
Editora / Evento / Instituição: Universidade Federal da Bahia
Sigla da Instituição: UFBA
metadata.dc.publisher.department: Instituto de Ciências da Saúde - ICS
metadata.dc.publisher.program: Programa de Pós-Graduação em Processos Interativos dos Órgãos e Sistemas (PPGORGSISTEM) 
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Tipo de Acesso: Acesso Aberto
URI: https://repositorio.ufba.br/handle/ri/34744
Data do documento: 26-Nov-2021
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