Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-08-10T11:14:59Z No. of bitstreams: 1 JoaoFelipeBezerra_TESE.pdf: 746132 bytes, checksum: eaa5510288612768dad80b3efbef567c (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-08-10T13:50:11Z (GMT) No. of bitstreams: 1 JoaoFelipeBezerra_TESE.pdf: 746132 bytes, checksum: eaa5510288612768dad80b3efbef567c (MD5) / Made available in DSpace on 2017-08-10T13:50:11Z (GMT). No. of bitstreams: 1 JoaoFelipeBezerra_TESE.pdf: 746132 bytes, checksum: eaa5510288612768dad80b3efbef567c (MD5) Previous issue date: 2017-04-03 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / As fendas orais constituem um problema de sa?de publica atingindo cerca de 15% de todas as malforma??es, caracterizando-se pela forma??o incompleta das estruturas que separam a cavidade nasal e a cavidade oral com fatores gen?ticos e ambientais que contribuem para sua etiologia. Atualmente, estudos de microarray, utilizando pacientes fissurados identificaram diversas regi?es de susceptibilidade para o desenvolvimento das fendas orais n?o-sindr?micas, dentre essas alguns estudos demonstraram a regi?o do gene Interferon Regulatory Factor 6 (IRF6) associado ao aumento de risco para o desenvolvimento das fendas. O objetivo do presente trabalho ? pesquisar polimorfismos do gene IRF6 e as poss?veis associa??es com o desenvolvimento das fendas orais n?o-sindr?micas. Para isso, um total de 368 individuos (186 pacientes FL/P e 182 controles) foram selecionados no Servi?o de Atendimento ao Paciente Fissurado - HUOL/UFRN. Amostras de sangue foram coletadas para extra??o do DNA e an?lise dos polimorfismos do gene IRF6 (rs2235371, rs642961, rs2236907, rs861019, e rs1044516) por PCR em tempo real. Os pacientes foram classificados nos grupos Fenda L?bio-palatina (CLP), Fenda labial (CL) e Fenda Palatina (CP) e foi observada uma associa??o significativa de rs2235371 (OR: 11,24, 95% CI: 1.97-64.22, p = 0,016) no grupo com a fendas palatinas isoladas (CP). Al?m disso, a an?lise da combina??o al?lica mostrou um aumento do risco de fendas associado aos polimorfismos rs1044516 e rs2236907, uma vez que estavam presentes em todas as combina??es significativas. Assim, a associa??o do rs2235371 com pacientes do grupo CP mostra-se como um fator de risco para CP em nossa popula??o. A an?lise das combina??es al?licas mostram a influ?ncia de polimorfismos do IRF6 combinadas, principalmente (rs1044516 e rs2236907) sugerem que cada polimorfismo pode contribuir minimamente para aumentar o risco de desenvolver fendas orais n?o-sindr?micas em uma popula??o brasileira de Rio Grande do Norte. / Orofacial clefts are a public health problem accounting for approximately 15% of all malformations, characterized by the incomplete formation of structures that separate the nasal cavity and oral cavity with genetic and environmental factors that contribute to its etiology. Currently, microarray studies using fissured patients have identified several regions of susceptibility to the development of non-syndromic orofacial clefts among which some studies have demonstrated the region of the Interferon Regulatory Factor 6 (IRF6) gene associated with increased risk for non-syndromic orofacial clefts development. The aim of the present study is to investigate polymorphisms of the IRF6 gene and the possible correlations with the development of non-syndromic orofacial clefts. For this, a total of 368 individuals (186 FL / P patients and 182 controls) were selected in the Service of the Fissured Patient - HUOL / UFRN. Blood samples were collected for DNA extraction and analysis of the polymorphisms of the IRF6 gene (rs2235371, rs642961, rs2236907, rs861019, and rs1044516) by real-time PCR. Patients were classified into the CLP, CL and CP groups and a significant association of rs2235371 (OR: 11.24, 95% CI: 1.97-64.22, p = 0.016) was observed in the group with isolated palate clefts (CP). In addition, the analysis of the allelic combination showed an increased risk orofacial clefts associated with the polymorphisms rs1044516 and rs2236907, since they were present in all significant combinations. Thus, the association of rs2235371 with patients in the CP group is shown as a risk factor for CP in our population. The analysis of allelic combinations show the influence of combined IRF6 polymorphisms mainly (rs1044516 and rs2236907) suggest that each polymorphism may contribute minimally to increase the risk of developing non-syndromic orofacial clefts in a Brazilian population of Rio Grande do Norte.