Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of Susceptibility to Cirrhosis Associated with Alcohol Abuse
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...
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doaj-abc172da2b0947b99693c2022f2ea2692020-11-24T21:27:38ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-07-012014358910.3390/ijms20143589ijms20143589Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of Susceptibility to Cirrhosis Associated with Alcohol AbuseKemper Nunes dos Santos0Rodrigo M. Florentino1Andressa França2Antônio Carlos Melo Lima Filho3Marcone Loiola dos Santos4Dabny Missiaggia5Matheus de Castro Fonseca6Igor Brasil Costa7Paula Vieira Teixeira Vidigal8Michael H. Nathanson9Fernanda de Oliveira Lemos10M. Fatima Leite11Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilLaboratório Nacional de Biociências (LNBio), Centro de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP 13083-970, BrazilInstituto de Pesquisas Evandro Chagas – IEC, Ananindeua, PA 67030-000, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilSection of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06510, USAUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilUniversidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, BrazilAlcoholic 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.https://www.mdpi.com/1422-0067/20/14/3589Alcoholic liver diseaseNrf2PolymorphismNFE2L2 gene |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kemper Nunes dos Santos Rodrigo M. Florentino Andressa França Antônio Carlos Melo Lima Filho Marcone Loiola dos Santos Dabny Missiaggia Matheus de Castro Fonseca Igor Brasil Costa Paula Vieira Teixeira Vidigal Michael H. Nathanson Fernanda de Oliveira Lemos M. Fatima Leite |
spellingShingle |
Kemper Nunes dos Santos Rodrigo M. Florentino Andressa França Antônio Carlos Melo Lima Filho Marcone Loiola dos Santos Dabny Missiaggia Matheus de Castro Fonseca Igor Brasil Costa Paula Vieira Teixeira Vidigal Michael H. Nathanson Fernanda de Oliveira Lemos M. Fatima Leite 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 Alcoholic liver disease Nrf2 Polymorphism NFE2L2 gene |
author_facet |
Kemper Nunes dos Santos Rodrigo M. Florentino Andressa França Antônio Carlos Melo Lima Filho Marcone Loiola dos Santos Dabny Missiaggia Matheus de Castro Fonseca Igor Brasil Costa Paula Vieira Teixeira Vidigal Michael H. Nathanson Fernanda de Oliveira Lemos M. Fatima Leite |
author_sort |
Kemper Nunes dos Santos |
title |
Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of Susceptibility to Cirrhosis Associated with Alcohol Abuse |
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 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-07-01 |
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. |
topic |
Alcoholic liver disease Nrf2 Polymorphism NFE2L2 gene |
url |
https://www.mdpi.com/1422-0067/20/14/3589 |
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