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Previous issue date: 2015-02-27 / O Diabetes Mellitus do tipo 1 (DM1) e uma doenca multifatorial, caracterizada pela destruicao autoimune das celulas ƒÀ pancreaticas. Alem do Antigeno Leucocitario Humano (HLA), varias regioes nao HLA foram descritas como importantes para o desenvolvimento da doenca, principalmente as que possuem efeito sobre o sistema imune. Dessa forma, este estudo objetivou avaliar a associacao de polimorfismos de base unica (SNPs) do gene da Interleucina-10 (IL-10), bem como seus niveis de expressao, na susceptibilidade ao DM1, correlacionar com o surgimento de doenca celiaca (DC) e tireoidite autoimune (AITD), e com a idade de diagnostico, em pacientes pernambucanos. Os SNPs estudados foram os rs1800896, rs1800871 e rs1800872, todos funcionais e localizados na regiao promotora do gene. Os ensaios de expressao e genotipagem foram realizados atraves de PCR em tempo real, com sondas TaqMan. O gene da IL 10 apresentou maiores niveis de expressao nos pacientes DM1 em relacao aos controles (p-value = 0,02), assim como na faixa etaria de 7 a 11 anos (p-value = 0,04), sendo mais expresso em pacientes com diagnostico de DM1 mais precoce. Com relacao aos SNPs, foi encontrada associacao do rs1800871 com o diagnostico tardio (p-value = 0,02). Nao foi encontrada associacao dos SNPs com a susceptibilidade ao DM1 ou dessa desordem associado a AITD e DC. Assim, esse estudo sugere a participacao da IL-10 na patogenese da doenca, contribuindo para o quadro inflamatorio de insulite, caracteristico do DM1. / Type 1 diabetes (T1D) is a multifactorial disease, characterized by autoimmune destruction of pancreatic insulin-producing â cells. Several non-HLA regions are described as being important for the development of the disease, and studies of genes in this region, especially having effect on the immune system, is being conducted. Thus, this study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) of Interleukin-10 (IL-10) gene, as well as its expression levels, with the development of T1D and other autoimmune diseases (celiac and autoimmune thyroiditis) and correlate with onset of T1D in a population of Brazilian northeast. The IL-10 SNPs studied were rs1800896, rs1800871 and rs1800872; all are functional and located in the promoter region of the gene. The assay genotyping of SNPs and gene expression was carried out by polymerase chain reaction (PCR) in real time, using TaqMan probes. The IL-10 gene was upregulated in T1D patients compared to controls (p-value 0.02). The same was observed in the group with higher age of T1D onset (p-value 0.04). Regarding to SNPs genotyping, it was found an association of rs1800871 with premature diagnosis (p-value 0.02). There was no association of SNPs with susceptibility to T1D, or the T1D associated with AITD and CD. Thus, this study suggests the involvement of IL-10 in the pathogenesis of the disease, contributing to the discovery of biomarkers for risk of T1D in our population.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufpe.br:123456789/15437 |
| Date | 27 February 2015 |
| Creators | LACERDA, Glaucia Alyne Nunes de |
| Contributors | GUIMARÃES, Rafael Lima |
| Publisher | UNIVERSIDADE FEDERAL DE PERNAMBUCO, Programa de Pos Graduacao em Saude Humana e Meio Ambiente, UFPE, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Breton |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFPE, instname:Universidade Federal de Pernambuco, instacron:UFPE |
| Rights | Attribution-NonCommercial-NoDerivs 3.0 Brazil, http://creativecommons.org/licenses/by-nc-nd/3.0/br/, info:eu-repo/semantics/openAccess |
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