Estudo De Associação Genética Em Larga Escala Identifica Potenciais Regiões Candidatas Para O Bruxismo Do Sono

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Estudo De Associação Genética Em Larga Escala Identifica Potenciais Regiões Candidatas Para O Bruxismo Do Sono Rosalvo Amaral Junior Estudo de associação genética em larga escala identifica potenciais regiões candidatas para o bruxismo do sono Dissertação apresentada à Universidade Federal de São Paulo – Escola Paulista de Medicina, para obtenção do Título de Mestre em Ciências São Paulo 2017 Rosalvo Amaral Junior Estudo de associação genética em larga escala identifica potenciais regiões candidatas para o bruxismo do sono Dissertação apresentada à Universidade Federal de São Paulo – Escola Paulista de Medicina, para obtenção do Título de Mestre em Ciências Orientadora: Profa. Dra. Monica Levy Andersen Coorientadora: Dra. Camila Hirotsu São Paulo 2017 Amaral Junior, Rosalvo Estudo de associação genética em larga escala identifica potenciais regiões candidatas para o bruxismo do sono/ Rosalvo Amaral Junior. São Paulo, 2017. xxiii, 100f. Dissertação (Mestrado) – Universidade Federal de São Paulo. Escola Paulista de Medicina. Programa de Pós -graduação em Psicobiologia. Título em inglês: Genome-wide association study identifies potential candidate gene regions for sleep bruxism. 1. Bruxismo do sono. 2. Genética. 3. Polimorfismo. 4. Polissonografia. Rosalvo Amaral Junior UNIVERSIDADE FEDERAL DE SÃO PAULO ESCOLA PAULISTA DE MEDICINA DEPARTAMENTO DE PSICOBIOLOGIA Chefe do Departamento: Prof. Dr. José Carlos Fernandes Galduróz Coordenadora do Curso de Pós-graduação: Profa. Dra. Débora Cristina Hipólide iii Rosalvo Amaral Junior Estudo de associação genética em larga escala identifica potenciais regiões candidatas para o bruxismo do sono Presidente da banca: Profa. Dra. Monica Levy Andersen BANCA EXAMINADORA Profa. Dra. Síntia Iole Nogueira Belangero Prof. Dr. José Tadeu Tesseroli de Siqueira Prof. Dr. Gustavo Antonio Moreira Aprovada em: 29/01/2017 iv Este estudo foi desenvolvido na seguinte instituição: Universidade Federal de São Paulo Escola Paulista de Medicina (UNIFESP/EPM) Departamento de Psicobiologia Disciplina de Medicina e Biologia do Sono Auxílio financeiro: Associação Fundo de Incentivo à Pesquisa (AFIP) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) v DEDICATÓRIA vi Dedico esta dissertação à Maria Ines Prado Lopes, que esteve ao meu lado durante a maior parte de minha vida e continua presente, apoiando meus projetos, criando com sabedoria nossos filhos Laura e Enzo, e cuidando com carinho de minha saúde física e mental. Minha melhor amiga. vii AGRADECIMENTOS viii Agradeço profundamente ao meu pai Rosalvo (In Memoriam) e à minha mãe Lourdes por me ensinarem com muita ênfase que o estudo pode proporcionar transformações e a oportunidade de construir um mundo melhor. Este ensinamento é um dos eixos de minha vida. Aos meus irmãos Maria Regina, Carlos Daniel, Rosângela e Marisa, seus filhos, netos e agregados. À família Bernini Amaral, exemplo de diversidade e respeito. À minha melhor amiga e ex-esposa Maria Ines Prado Lopes. Consegui chegar até aqui porque ela dividiu comigo sua energia. Amparou-me nos momentos difíceis. Comemorou as conquistas. Incentivou a procurar outros rumos. Despertou-me para novas dimensões. Mostrou horizontes muito além do que eu podia enxergar. Muito, muito obrigado. Aos meus filhos Maria Carolina, Laura e Enzo, que talvez ainda não saibam ou percebam o quanto me ensinam. Cada um ao seu modo me ajuda a escrever meu currículo de vida enquanto escrevem os seus. À Profa. Dra. Monica Levy Andersen, que inspirou e motivou este Mestrado desde o princípio. Que o tornou realidade me aceitando como aluno. Que me acolheu quando a vida me interrogou. Sou admirador de suas aulas, carreira profissional e história; de sua orientação científica e de sua orientação para a vida; de seu trato com as pessoas e especialmente sua capacidade de estimular em cada um as virtudes e de fazer refletir sobre as atitudes. O título de professora e cientista está estampado em sua presença. À minha coorientadora Dra. Camila Hirotsu. Consolidamos nossa amizade ao compartilharmos este trabalho. Como se me ensinasse a escrever minhas primeiras palavras estimulou meu raciocínio e minha atividade científica. Com uma paciência especial respondeu todas as dúvidas. Estimulou a pesquisa. Sacudiu meu acomodamento. Ensinou-me a confiar mais em mim. Parceria estabelecida para sempre. Ao Dr. Diego Robles Mazzotti, por ter facilitado o estudo da genética com seus ensinamentos e orientações. Sua atuação foi especial e decisiva para a concretização do Mestrado. Seu espírito científico e inovador e sua capacidade didática o torna merecedor da carreira de sucesso construída. ix Ao Prof. Dr. Sergio Tufik, pela magnífica obra que vislumbrou, construiu e continua edificando e que permitiu tornar real este e tantos outros projetos. Ao grupo Progressão, jovens cientistas entusiasmados e competentes, pelo auxílio cotidiano a um estudante não tão jovem. Especialmente gostaria de agradecer à Lenise Kim que com sua amizade e generosidade tornaram mais fáceis a superação de muitos obstáculos e a ter momentos prazerosos de bate-papo. Especial também foi a amizade de Cristina Frange que carinhosamente dedicou sua atenção especial em momentos muito difíceis. Camila Hirotsu, Gabriel Pires, Andréia Bezerra, Paula Araujo, Tathiana Alvarenga, Daniel Polesel, Karen Nozoe, Rachel Albuquerque, John Helbert, Luísa de Barros, Daniela Oliveira, Priscila Tempaku, Vinícius Silva: sou um privilegiado por ter tido a oportunidade de conviver com todos vocês. A todos os funcionários da Unifesp, profissionais que admiro e que às vezes anonimamente conduzem a vida da instituição. Waldermaks Aires (Dunga), Mara Viana, Valéria Acquilino, Maria de Oliveira: muito obrigado pelo sorriso com que sempre fui recebido. Aos meus amigos Fabian, Nelson e Assis que pelo menos semanalmente me lembra do quanto é importante lutar pela construção de um mundo mais justo, solidário e fraterno. Às agências de fomento Fapesp, CNPq, Afip e Capes, pelo importante apoio financeiro que possibilitou a execução deste trabalho. x "Para quem vive em busca do sol, é sempre madrugada." Helena Kolody Poesia mínima xi SUMÁRIO xii DEDICATÓRIA ............................................................................................................................................. vi AGRADECIMENTOS ................................................................................................................................. viii SUMÁRIO .................................................................................................................................................... xii LISTAS ....................................................................................................................................................... xiv RESUMO ..................................................................................................................................................... xx 1 INTRODUÇÃO ............................................................................................................................... 01 1.1 Bruxismo do sono ........................................................................................................................... 02 1.2 Epidemiologia do bruxismo do sono .............................................................................................. 03 1.3 Etiologia e fisiopatologia do bruxismo do sono .............................................................................. 04 1.4 Genética e o bruxismo do sono ...................................................................................................... 13 2 RELEVÂNCIA ................................................................................................................................. 16 3 OBJETIVOS ................................................................................................................................... 18 3.1 Objetivo geral.................................................................................................................................. 19 3.2 Objetivos específicos ...................................................................................................................... 19 4 MATERIAL E MÉTODOS ............................................................................................................... 20 4.1 Métodos .......................................................................................................................................... 21 4.1.1 Seleção dos voluntários .......................................................................................................... 21 4.1.2 Polissonografia ....................................................................................................................... 22 4.1.3 Diagnóstico do bruxismo do sono ........................................................................................... 23 4.1.4 Questionários .......................................................................................................................... 24 4.1.5 Avaliações Genéticas ............................................................................................................. 25 4.1.6 Análise estatística ................................................................................................................... 25 5 RESULTADOS ............................................................................................................................... 30 6 DISCUSSÃO .................................................................................................................................
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