Made available in DSpace on 2014-12-17T15:18:09Z (GMT). No. of bitstreams: 1
ThayseAS.pdf: 421769 bytes, checksum: da81d1c89c2fb11516509aaaad4a2595 (MD5)
Previous issue date: 2008-04-08 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Despite advances in vaccine development and therapy, bacterial meningitis (BM) remains a major cause of death and long-term neurological disabilities. As part of the host inflammatory response to the invading pathogen, factors such as reactive oxygen species are generated, which may damage DNA and trigger the overactivation of DNA repair mechanisms. It is conceivable that the individual susceptibility and outcome of BM may be in part determined by non synonymous polymorphisms that may alter the function of crucial BER DNA repair enzymes as PARP-1, OGG-1 and APE-1. These enzymes, in addition to their important DNA repair function, also perform role of inflammatory regulators. In this work was investigated the non synonymous SNPs APE-1 Asn148Glu, OGG-1 Ser326Cys,PARP-1 Val762Ala, PARP-1 Pro882Leu and PARP-1 Cys908Tyr in patients with bacterial meningitis (BM), chronic meningitis (CM), aseptic meningitis (AM) and not infected (controls). As results we found increased frequency of variant alleles of PARP-1 Val762Ala (P = 0.005) and APE-1 Asn148Glu (P=0.018) in BM patients, APE-1 Asn148Glu in AM patients (P = 0.012) and decrease in the frequency of the variant allele OGG-1 Ser326Cys in patients with CM (P = 0.013), regarding the allelic frequencies in the controls. A major incidence of individuals heterozygous and/ or polymorphic homozygous in BM for PARP-1 Val762Ala (P= 0.0399, OD 4.2, 95% IC 1.213 -14.545) and PARP-1 Val762Ala/ APE-1 Asn148Glu (P = 0.0238, OD 11.111, 95% IC 1.274 - 96.914) was observed related to what was expected in a not infected population. It was also observed a major incidence of combined SNPs in the BM patients compared with the control group (P=0.0281), giving evidences that SNPs can cause some susceptibility to the disease. This combined effect of SNPs seems to regulate the principal cytokines and other factors related to BM inflammatory response and point the importance of DNA repair not only to repair activity when DNA is damaged, but to others essential functions to human organism balance. / Apesar dos avan?os no desenvolvimento de vacinas e terapias, a meningite bacteriana (MB) continua sendo uma das principais causas de morte e seq?elas neurol?gicas causadas por uma doen?a infecciosa. Como parte da resposta
inflamat?ria ao pat?geno invasor, fatores como esp?cies reativas de oxig?nio (ROS) s?o geradas, podendo causar danos no DNA e ativar seus mecanismos de repara??o. ? poss?vel que a susceptibilidade individual do hospedeiro ? MB possa ser em parte determinada por polimorfismos n?o-sin?nimos (SNPs) que possivelmente alterem a fun??o de enzimas de reparo de DNA da via BER como PARP-1, OGG-1 e APE-1. Estas enzimas, al?m da importante fun??o na corre??o de danos no DNA, tamb?m desempenham papel de reguladores inflamat?rios. Neste trabalho foram investigados os SNPs n?o-sin?nimos APE-1 Asn148Glu, OGG-1 Ser326Cys, PARP-1 Val762Ala, PARP-1 Pro882Leu e PARP-1 Cys908Tyr em
pacientes com meningite bacteriana (MB), meningite cr?nica (MC), meningite ass?ptica (MA) e n?o infectados (controles). Como resultado, foi encontrado um aumento na freq??ncia dos alelos variantes de PARP-1 Val762Ala (P = 0.005) e
APE-1 Asn148Glu (P=0.018) em pacientes com MB, de APE-1 Asn148Glu em pacientes com MA (P = 0.012) e diminui??o da freq??ncia do alelo variante OGG1 Ser326Cys (P = 0.013) em pacientes com MC em rela??o ?s freq??ncias al?licas observada nos controles para estes polimorfismos. Foi observado um maior n?mero de indiv?duos heterozigotos e/ou homozigotos polim?rficos para os gen?tipos polim?rficos PARP-1 Val762Ala (P= 0.0399, OD 4.2, 95% IC 1.213 -14.545) e PARP-1 Val762Ala/ APE-1 Asn148Glu (P = 0.0238, OD 11.111, 95% IC 1.274 - 96.914) no grupo MB em rela??o ao que se era esperado dentro de uma popula??o n?o-infectada. Observou-se tamb?m uma maior incid?ncia de SNPs combinados em pacientes com MB quando comparado ao grupo controle. Estas rela??es trazem evid?ncias de que os SNPs analisados causam alguma susceptibilidade ? doen?a. O
efeito combinado destes SNPs parece influenciar a regula??o das principais citocinas e de outros fatores relacionados com a resposta inflamat?ria a MB, mostrando a import?ncia da ativa??o de enzimas de reparo de DNA n?o somente
quando o DNA ? danificado, mas para outras fun??es essenciais ao equil?brio do organismo humano.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/16759 |
| Date | 08 April 2008 |
| Creators | Silva, Thayse Azevedo da |
| Contributors | CPF:00297997750, http://lattes.cnpq.br/1083882171718362, Uchoa, Adriana Ferreira, CPF:58024867320, http://lattes.cnpq.br/6644671747055211, Hutz, Mara Helena, CPF:28018311072, HUTZ, Mara Helena, Lima, Lucymara Fassarela Agnez |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Gen?tica e Biologia Molecular, UFRN, BR, Gen?tica e Biologia Molecular |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
Page generated in 0.0028 seconds