Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of Susceptibility to Cirrhosis Associated with Alcohol Abuse

Autor(es):Mostrar menos -

dos Santos, Kemper Nunes ^[1] ; Florentino, Rodrigo M. ^[1] ; Franca, Andressa ^[1] ; Melo Lima Filho, Antonio Carlos ^[1] ; dos Santos, Marcone Loiola ^[1] ; Missiaggia, Dabny ^[1] ; Fonseca, Matheus de Castro ^[2] ; Costa, Igor Brasil ^[3] ; Teixeira Vidigal, Paula Vieira ^[1] ; Nathanson, Michael H. ^[4] ; Lemos, Fernanda de Oliveira ^[1] ; Fatima Leite, M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Ctr Pesquisa Energia & Mat CNPEM, Lab Nacl Biociencias LNBio, BR-13083970 Campinas, SP - Brazil

^[3] Inst Pesquisas Evandro Chagas IEC, BR-67030000 Ananindeua, PA - Brazil

^[4] Yale Univ, Sch Med, Sect Digest Dis, 333 Cedar St, New Haven, CT 06510 - USA

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 14 JUL 2 2019.
• Citações Web of Science: 0

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. (AU)

• Processo FAPESP: 18/20014-0 - Conectando o intestino e o cérebro: envolvimento do microbioma intestinal no surgimento e progressão da doença de Parkinson esporádica
• Beneficiário: Matheus de Castro Fonseca
• Modalidade de apoio: Auxílio à Pesquisa - Regular