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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2012.tde-09112012-105715
Document
Author
Full name
Alexandre La Luna
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Krieger, Henrique (President)
Gruber, Arthur
Lyra, André Castro
Pinho, João Renato Rebello
Simões, Aguinaldo Luiz
Title in Portuguese
Busca de fatores genéticos associados à resposta ao tratamento do HCV genótipo 3.
Keywords in Portuguese
Epidemiologia (Genética)
Hepatite C
Interferons
Abstract in Portuguese
Recentemente estudos demonstraram que os SNPs (polimorfismos de base única) rs8099917 e rs12979860 localizados próximos ao gene da IL28B explicam a variação de resposta à infecção e tratamento do paciente contra o genótipo 1 do HCV, porém não para o genótipo 3 deste vírus. Este trabalho encontrou associação significativa entre resposta à infecção devida ao genótipo 3 pelo tratamento (PEG-INF e RBV) e o polimorfismo rs8099917 em uma amostra da população de Santos - SP. Para o polimorfismo rs12979860, esta associação somente foi encontrada ao se parear indivíduos para sexo, idade e grau de fibrose hepática, demonstrando a importância da retirada de efeitos de estratificação neste tipo de análise. Estes resultados se confirmam ao se agregar dados de uma população proveniente da Bahia em uma meta-análise. Além disso, fez-se um estudo GWAS a fim de se conhecer outras variações genéticas envolvidas nessa resposta. Esta análise indicou a existência de alguns SNPs candidatos com sugestão de associação, dentre eles a tiroglobulina, relacionada aos hormônios da tireóide.
Title in English
Search for genetic factors associated with treatment response in HCV genotype 3.
Keywords in English
Epidemiology (Genetics)
Hepatitis C
Interferons
Abstract in English
Recently, studies have shown that SNPs (single nucleotide polymorphisms) rs8099917 and rs12979860, located near the gene IL28B explain the changes in the response to infection and treatment of a patient against the HCV genotype 1, but not for the genotype 3 of the virus. This study found a significant association between response to infection due to treatment by genotype 3 (PEG-INF and RBV) and the rs8099917 polymorphism in a population sample from Santos - SP. To the rs12979860 polymorphism, this association was only found when individuals are paired for sex, age and degree of hepatic fibrosis, demonstrating the importance of the withdrawal effects of stratification in this type of analysis. These results confirm the aggregate data from a population of Bahia in a meta-analysis. In addition, a GWAS was made in order to search other genetic variations involved in this response. This analysis indicated the existence of some candidate SNPs with suggestion of association, including thyroglobulin, thyroid hormones related to.
 
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Publishing Date
2013-02-08
 
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