Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil
Ano de defesa: | 2013 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Uberlândia
|
Programa de Pós-Graduação: |
Programa de Pós-graduação em Ciências da Saúde
|
Departamento: |
Ciências da Saúde
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | https://repositorio.ufu.br/handle/123456789/12759 https://doi.org/10.14393/ufu.di.2013.37 |
Resumo: | Objective: The mthfr (methylenetetrahydrofolate reductase) gene has a strong impact on DNA methylation, biosynthesis and repair of proliferating cells, and its most common mutation (C677T) has been linked to a reduced enzymatic activity, and consequently involved in various inflammatory diseases probably due to the homocysteine accumulation (Hcy). Methotrexate (MTX) is an antifolate agent widely used as a disease-modifying anti-rheumatic drug (DMARD) for treatment of juvenile idiopathic arthritis (JIA). The objective is to analyze the association between allelic and genotypic distribution of the C677T polymorphism of the gene encoding MTHFR and susceptibility to JIA. Method: A cross-sectional study included 38 patients with JIA and 22 healthy controls, with age range from 3 to 22 years. JIA patients were under MTX treatment, and were monitored for adverse events. Laboratorial analyses and clinical examinations, including toxicity data, were performed during 16 months. Patients underwent peripheral blood sampling for DNA extraction and subsequent analysis by Polymerase Chain Reaction and Sequencing to determine if there were changes in the amplified region. Results: JIA occurrence was significantly associated with the 677T allele and its genotypes (P<0.01). The odds ratios for T allele and genotypes (CT and TT) were eight-times higher towards the disease manifestation, suggesting a dominance effect of the T allele. There was no significant correlation between the C677T polymorphism and laboratorialy analyses and medical history (p>0.05), which was not associated with adverse reactions to MTX therapy (p>0.05) either. We found a new polymorphism was 678 not yet described in the literature. Conclusion: JIA was significantly affected by the polymorphism in the MTHFR gene at the C677T genomic region. The increased prevalence of CT and TT genotypes in JIA patients indicated a dominance effect of the T allele. However, this polymorphism was not associated with MTX intolerance, suggesting that accumulation of substrate is not related to the incapacity of patients to sequester MTX and prevent cellular detoxification. |
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2016-06-22T18:33:11Z2013-07-052016-06-22T18:33:11Z2013-02-18AGUIAR, Ayla Dayane de Faria. Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil. 2013. 88 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2013. DOI https://doi.org/10.14393/ufu.di.2013.37https://repositorio.ufu.br/handle/123456789/12759https://doi.org/10.14393/ufu.di.2013.37Objective: The mthfr (methylenetetrahydrofolate reductase) gene has a strong impact on DNA methylation, biosynthesis and repair of proliferating cells, and its most common mutation (C677T) has been linked to a reduced enzymatic activity, and consequently involved in various inflammatory diseases probably due to the homocysteine accumulation (Hcy). Methotrexate (MTX) is an antifolate agent widely used as a disease-modifying anti-rheumatic drug (DMARD) for treatment of juvenile idiopathic arthritis (JIA). The objective is to analyze the association between allelic and genotypic distribution of the C677T polymorphism of the gene encoding MTHFR and susceptibility to JIA. Method: A cross-sectional study included 38 patients with JIA and 22 healthy controls, with age range from 3 to 22 years. JIA patients were under MTX treatment, and were monitored for adverse events. Laboratorial analyses and clinical examinations, including toxicity data, were performed during 16 months. Patients underwent peripheral blood sampling for DNA extraction and subsequent analysis by Polymerase Chain Reaction and Sequencing to determine if there were changes in the amplified region. Results: JIA occurrence was significantly associated with the 677T allele and its genotypes (P<0.01). The odds ratios for T allele and genotypes (CT and TT) were eight-times higher towards the disease manifestation, suggesting a dominance effect of the T allele. There was no significant correlation between the C677T polymorphism and laboratorialy analyses and medical history (p>0.05), which was not associated with adverse reactions to MTX therapy (p>0.05) either. We found a new polymorphism was 678 not yet described in the literature. Conclusion: JIA was significantly affected by the polymorphism in the MTHFR gene at the C677T genomic region. The increased prevalence of CT and TT genotypes in JIA patients indicated a dominance effect of the T allele. However, this polymorphism was not associated with MTX intolerance, suggesting that accumulation of substrate is not related to the incapacity of patients to sequester MTX and prevent cellular detoxification.Objetivo: O gene mthfr (metilenotetrahidrofolato redutase) tem um forte impacto sobre a metilação do DNA, a biossíntese e reparação de células em proliferação, e a sua mutação mais frequente (C677T) tem sido associada a uma redução da atividade enzimática, e, consequentemente, envolvida em diversas doenças inflamatórias, provavelmente devido ao acúmulo de homocisteína (Hcy). O metotrexato (MTX) é um agente antifolato amplamente utilizado como uma droga antirreumática modificadora de doença (DMARD) para o tratamento da Artrite Idiopática Juvenil (AIJ). O objetivo é analisar a associação entre a distribuição alélica e genotípica do polimorfismo C677T do gene codificador da enzima MTHFR e a susceptibilidade à AIJ. Método: Estudo transversal com 38 pacientes com AIJ e 22 controles saudáveis, com faixa etária entre 3 a 22 anos. Pacientes com AIJ foram tratados com MTX, e foram monitorados para a ocorrência de eventos adversos. Análises laboratoriais e exames clínicos, incluindo dados de toxicidade, foram realizados durante 16 meses. Pacientes foram submetidos à coleta de sangue periférico para extração de DNA e posterior análise por Reação em Cadeia da Polimerase e Sequenciamento para determinar se havia modificação na região amplificada. Resultados: A ocorrência de AIJ foi significativamente associada com o alelo 677T e seus genótipos (p<0.01). O odds ratio para o alelo T e genótipos (CT e TT) foi oito vezes maior para a manifestação da doença, o que sugere um efeito de dominância do alelo T. Não houve correlação significativa entre o polimorfismo C677T e análises laboratoriais e história clínica (p>0.05), o que também não foi associado com reações adversas ao tratamento com MTX (p>0.05). Foi encontrado um novo polimorfismo na região 678 ainda não descrito na literatura. Conclusão: A AIJ foi significativamente afetada pelo polimorfismo no gene MTHFR na região genômica C677T. O aumento da prevalência de genótipos CT e TT em pacientes com AIJ indicou um efeito de dominância do alelo T. No entanto, este polimorfismo não estava associado com intolerância MTX, o que sugere que o acúmulo de substrato não está relacionado com a incapacidade do paciente para sequestrar MTX e prevenir a desintoxicação celular.Mestre em Ciências da Saúdeapplication/pdfporUniversidade Federal de UberlândiaPrograma de Pós-graduação em Ciências da SaúdeUFUBRCiências da SaúdeArtrite idiopática juvenilMetotrexatoPolimorfismo genéticoToxicidadeSusceptibilidadeMetilenotetrahidrofolato redutasePolimorfismo (Genética)Juvenile idiopathic arthritisMethotrexateGenetic polymorphismToxicitySusceptibilityMethylenetetrahydrofolate reductaseCNPQ::CIENCIAS DA SAUDEAssociação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenilinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMaia, Yara Cristina de Paivahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133677P3Ueira-Vieira, Carloshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4706664A7Crispim, Cibele Aparecidahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4773956J5Oliveira, Rosana de Cássiahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4792884E1http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4128543J7Aguiar, Ayla Dayane de Faria81758046info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFUTHUMBNAILAyla Dayane.pdf.jpgAyla Dayane.pdf.jpgGenerated Thumbnailimage/jpeg1189https://repositorio.ufu.br/bitstream/123456789/12759/3/Ayla%20Dayane.pdf.jpg4fc3c456102b8eee9131e0bb6b7c6325MD53ORIGINALAyla Dayane.pdfapplication/pdf1929564https://repositorio.ufu.br/bitstream/123456789/12759/1/Ayla%20Dayane.pdf5e8d3e9900808aa0f13adde5f63fbc10MD51TEXTAyla Dayane.pdf.txtAyla Dayane.pdf.txtExtracted texttext/plain144187https://repositorio.ufu.br/bitstream/123456789/12759/2/Ayla%20Dayane.pdf.txta33bd0fc5c0f00a2df2d3ac455bc2cf5MD52123456789/127592022-08-10 15:12:50.303oai:repositorio.ufu.br:123456789/12759Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2022-08-10T18:12:50Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false |
dc.title.por.fl_str_mv |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
title |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
spellingShingle |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil Aguiar, Ayla Dayane de Faria Artrite idiopática juvenil Metotrexato Polimorfismo genético Toxicidade Susceptibilidade Metilenotetrahidrofolato redutase Polimorfismo (Genética) Juvenile idiopathic arthritis Methotrexate Genetic polymorphism Toxicity Susceptibility Methylenetetrahydrofolate reductase CNPQ::CIENCIAS DA SAUDE |
title_short |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
title_full |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
title_fullStr |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
title_full_unstemmed |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
title_sort |
Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil |
author |
Aguiar, Ayla Dayane de Faria |
author_facet |
Aguiar, Ayla Dayane de Faria |
author_role |
author |
dc.contributor.advisor-co1.fl_str_mv |
Maia, Yara Cristina de Paiva |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133677P3 |
dc.contributor.advisor1.fl_str_mv |
Ueira-Vieira, Carlos |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4706664A7 |
dc.contributor.referee1.fl_str_mv |
Crispim, Cibele Aparecida |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4773956J5 |
dc.contributor.referee2.fl_str_mv |
Oliveira, Rosana de Cássia |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4792884E1 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4128543J7 |
dc.contributor.author.fl_str_mv |
Aguiar, Ayla Dayane de Faria |
contributor_str_mv |
Maia, Yara Cristina de Paiva Ueira-Vieira, Carlos Crispim, Cibele Aparecida Oliveira, Rosana de Cássia |
dc.subject.por.fl_str_mv |
Artrite idiopática juvenil Metotrexato Polimorfismo genético Toxicidade Susceptibilidade Metilenotetrahidrofolato redutase Polimorfismo (Genética) |
topic |
Artrite idiopática juvenil Metotrexato Polimorfismo genético Toxicidade Susceptibilidade Metilenotetrahidrofolato redutase Polimorfismo (Genética) Juvenile idiopathic arthritis Methotrexate Genetic polymorphism Toxicity Susceptibility Methylenetetrahydrofolate reductase CNPQ::CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Juvenile idiopathic arthritis Methotrexate Genetic polymorphism Toxicity Susceptibility Methylenetetrahydrofolate reductase |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE |
description |
Objective: The mthfr (methylenetetrahydrofolate reductase) gene has a strong impact on DNA methylation, biosynthesis and repair of proliferating cells, and its most common mutation (C677T) has been linked to a reduced enzymatic activity, and consequently involved in various inflammatory diseases probably due to the homocysteine accumulation (Hcy). Methotrexate (MTX) is an antifolate agent widely used as a disease-modifying anti-rheumatic drug (DMARD) for treatment of juvenile idiopathic arthritis (JIA). The objective is to analyze the association between allelic and genotypic distribution of the C677T polymorphism of the gene encoding MTHFR and susceptibility to JIA. Method: A cross-sectional study included 38 patients with JIA and 22 healthy controls, with age range from 3 to 22 years. JIA patients were under MTX treatment, and were monitored for adverse events. Laboratorial analyses and clinical examinations, including toxicity data, were performed during 16 months. Patients underwent peripheral blood sampling for DNA extraction and subsequent analysis by Polymerase Chain Reaction and Sequencing to determine if there were changes in the amplified region. Results: JIA occurrence was significantly associated with the 677T allele and its genotypes (P<0.01). The odds ratios for T allele and genotypes (CT and TT) were eight-times higher towards the disease manifestation, suggesting a dominance effect of the T allele. There was no significant correlation between the C677T polymorphism and laboratorialy analyses and medical history (p>0.05), which was not associated with adverse reactions to MTX therapy (p>0.05) either. We found a new polymorphism was 678 not yet described in the literature. Conclusion: JIA was significantly affected by the polymorphism in the MTHFR gene at the C677T genomic region. The increased prevalence of CT and TT genotypes in JIA patients indicated a dominance effect of the T allele. However, this polymorphism was not associated with MTX intolerance, suggesting that accumulation of substrate is not related to the incapacity of patients to sequester MTX and prevent cellular detoxification. |
publishDate |
2013 |
dc.date.available.fl_str_mv |
2013-07-05 2016-06-22T18:33:11Z |
dc.date.issued.fl_str_mv |
2013-02-18 |
dc.date.accessioned.fl_str_mv |
2016-06-22T18:33:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
AGUIAR, Ayla Dayane de Faria. Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil. 2013. 88 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2013. DOI https://doi.org/10.14393/ufu.di.2013.37 |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufu.br/handle/123456789/12759 |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.14393/ufu.di.2013.37 |
identifier_str_mv |
AGUIAR, Ayla Dayane de Faria. Associação do polimorfismo no gene codificador da enzima MTHFR com a artrite idiopática juvenil. 2013. 88 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2013. DOI https://doi.org/10.14393/ufu.di.2013.37 |
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https://repositorio.ufu.br/handle/123456789/12759 https://doi.org/10.14393/ufu.di.2013.37 |
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Universidade Federal de Uberlândia |
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Programa de Pós-graduação em Ciências da Saúde |
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UFU |
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BR |
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Ciências da Saúde |
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Universidade Federal de Uberlândia |
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