Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse

Detalhes bibliográficos
Autor(a) principal: Santos, Kemper Nunes dos
Data de Publicação: 2019
Outros Autores: Florentino, Rodrigo M, França, Andressa, Lima Filho, Antônio Carlos Melo, Santos, Marcone Lisboa dos, Missiaggia, Dabny, Fonseca, Matheus de Castro, Costa, Igor Brasil, Vidigal, Paula Vieira Teixeira, Nathanson, Michael H, Lemos, Fernanda de Oliveira, Leite, M. Fatima
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/3825
Resumo: Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.
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spelling Santos, Kemper Nunes dosFlorentino, Rodrigo MFrança, AndressaLima Filho, Antônio Carlos MeloSantos, Marcone Lisboa dosMissiaggia, DabnyFonseca, Matheus de CastroCosta, Igor BrasilVidigal, Paula Vieira TeixeiraNathanson, Michael HLemos, Fernanda de OliveiraLeite, M. Fatima2019-08-12T12:05:45Z2019-08-12T12:05:45Z2019SANTOS, Kemper Nunes dos et al. Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse. International Journal of Molecular Sciences, v. 20, n. 14, e3589, p. 1-14, July 2019.1422-0067https://patua.iec.gov.br/handle/iec/382510.3390/ijms20143589Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 159892/2018-0), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal (CAPES), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2018/20014-0), Liver Center at UFMG, NIH (DK57751, DK34989, DK114041, and DK112797 to MHN). This work also was supported by the Gladys Phillips Crofoot Professorship.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Centro de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.Yale University School of Medicine. Section of Digestive Diseases. New Haven, CT, USA.engMDPIPolymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFígado / anatomia & histologiaCirrose Hepática / patologiaFator 2 Relacionado a NF-E2 / genéticaAlcoolismo / diagnósticoGenes / imunologiaPolimorfismo Genético / imunologiaMarcadores Genéticosinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALPolymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse.pdfPolymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse.pdfapplication/pdf2040675https://patua.iec.gov.br/bitstreams/89b3b028-f36c-4a39-923f-db769bd642ab/downloadc9d9d7d1532fd774ab4fdcb46f9699e3MD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
title Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
spellingShingle Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
Santos, Kemper Nunes dos
Fígado / anatomia & histologia
Cirrose Hepática / patologia
Fator 2 Relacionado a NF-E2 / genética
Alcoolismo / diagnóstico
Genes / imunologia
Polimorfismo Genético / imunologia
Marcadores Genéticos
title_short Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
title_full Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
title_fullStr Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
title_full_unstemmed Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
title_sort Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse
author Santos, Kemper Nunes dos
author_facet Santos, Kemper Nunes dos
Florentino, Rodrigo M
França, Andressa
Lima Filho, Antônio Carlos Melo
Santos, Marcone Lisboa dos
Missiaggia, Dabny
Fonseca, Matheus de Castro
Costa, Igor Brasil
Vidigal, Paula Vieira Teixeira
Nathanson, Michael H
Lemos, Fernanda de Oliveira
Leite, M. Fatima
author_role author
author2 Florentino, Rodrigo M
França, Andressa
Lima Filho, Antônio Carlos Melo
Santos, Marcone Lisboa dos
Missiaggia, Dabny
Fonseca, Matheus de Castro
Costa, Igor Brasil
Vidigal, Paula Vieira Teixeira
Nathanson, Michael H
Lemos, Fernanda de Oliveira
Leite, M. Fatima
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos, Kemper Nunes dos
Florentino, Rodrigo M
França, Andressa
Lima Filho, Antônio Carlos Melo
Santos, Marcone Lisboa dos
Missiaggia, Dabny
Fonseca, Matheus de Castro
Costa, Igor Brasil
Vidigal, Paula Vieira Teixeira
Nathanson, Michael H
Lemos, Fernanda de Oliveira
Leite, M. Fatima
dc.subject.decsPrimary.pt_BR.fl_str_mv Fígado / anatomia & histologia
Cirrose Hepática / patologia
Fator 2 Relacionado a NF-E2 / genética
Alcoolismo / diagnóstico
Genes / imunologia
Polimorfismo Genético / imunologia
Marcadores Genéticos
topic Fígado / anatomia & histologia
Cirrose Hepática / patologia
Fator 2 Relacionado a NF-E2 / genética
Alcoolismo / diagnóstico
Genes / imunologia
Polimorfismo Genético / imunologia
Marcadores Genéticos
description Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-08-12T12:05:45Z
dc.date.available.fl_str_mv 2019-08-12T12:05:45Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SANTOS, Kemper Nunes dos et al. Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse. International Journal of Molecular Sciences, v. 20, n. 14, e3589, p. 1-14, July 2019.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/3825
dc.identifier.issn.-.fl_str_mv 1422-0067
dc.identifier.doi.-.fl_str_mv 10.3390/ijms20143589
identifier_str_mv SANTOS, Kemper Nunes dos et al. Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse. International Journal of Molecular Sciences, v. 20, n. 14, e3589, p. 1-14, July 2019.
1422-0067
10.3390/ijms20143589
url https://patua.iec.gov.br/handle/iec/3825
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv MDPI
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reponame_str Repositório Digital do Instituto Evandro Chagas (Patuá)
collection Repositório Digital do Instituto Evandro Chagas (Patuá)
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