PMID- 31340446
OWN - NLM
STAT- MEDLINE
DCOM- 20191227
LR  - 20231104
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 14
DP  - 2019 Jul 23
TI  - Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of 
      Susceptibility to Cirrhosis Associated with Alcohol Abuse.
LID - 10.3390/ijms20143589 [doi]
LID - 3589
AB  - 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.
FAU - Nunes Dos Santos, Kemper
AU  - Nunes Dos Santos K
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Florentino, Rodrigo M
AU  - Florentino RM
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Franca, Andressa
AU  - Franca A
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Lima Filho, Antonio Carlos Melo
AU  - Lima Filho ACM
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Santos, Marcone Loiola Dos
AU  - Santos MLD
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Missiaggia, Dabny
AU  - Missiaggia D
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Fonseca, Matheus de Castro
AU  - Fonseca MC
AUID- ORCID: 0000-0001-9048-9775
AD  - Laboratorio Nacional de Biociencias (LNBio), Centro de Pesquisa em Energia e 
      Materiais (CNPEM), Campinas, SP 13083-970, Brazil.
FAU - Brasil Costa, Igor
AU  - Brasil Costa I
AD  - Instituto de Pesquisas Evandro Chagas - IEC, Ananindeua, PA 67030-000, Brazil.
FAU - Vidigal, Paula Vieira Teixeira
AU  - Vidigal PVT
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
FAU - Nathanson, Michael H
AU  - Nathanson MH
AD  - Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 
      06510, USA.
FAU - Lemos, Fernanda de Oliveira
AU  - Lemos FO
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil. 
      folemos@hotmail.com.
FAU - Leite, M Fatima
AU  - Leite MF
AD  - Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
LA  - eng
GR  - 159892/2018-0/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - P01 DK057751/DK/NIDDK NIH HHS/United States
GR  - x/Liver Center at UFMG/
GR  - P30 DK034989/DK/NIDDK NIH HHS/United States
GR  - R01 DK112797/DK/NIDDK NIH HHS/United States
GR  - x/Fundacao de Amparo a Pesquisa de Minas Gerais/
GR  - R01 DK114041/DK/NIDDK NIH HHS/United States
GR  - x/Coordenacao de Aperfeicoamento de Pessoal/
GR  - 2018/20014-0/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
PT  - Journal Article
DEP - 20190723
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Ethanol/pharmacology
MH  - Female
MH  - Gene Expression
MH  - *Genetic Predisposition to Disease
MH  - Hepacivirus/growth & development/pathogenicity
MH  - Hepatitis C/pathology/virology
MH  - Humans
MH  - Liver/drug effects/metabolism/pathology
MH  - Liver Cirrhosis, Alcoholic/*genetics/metabolism/pathology/surgery
MH  - Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - NF-E2-Related Factor 2/*genetics
MH  - Oxidative Stress
MH  - *Polymorphism, Single Nucleotide
MH  - *Promoter Regions, Genetic
PMC - PMC6678089
OTO - NOTNLM
OT  - Alcoholic liver disease
OT  - NFE2L2 gene
OT  - Nrf2
OT  - Polymorphism
COIS- The authors declare no conflict of interest.
EDAT- 2019/07/26 06:00
MHDA- 2019/12/28 06:00
PMCR- 2019/07/01
CRDT- 2019/07/26 06:00
PHST- 2019/06/19 00:00 [received]
PHST- 2019/07/12 00:00 [revised]
PHST- 2019/07/15 00:00 [accepted]
PHST- 2019/07/26 06:00 [entrez]
PHST- 2019/07/26 06:00 [pubmed]
PHST- 2019/12/28 06:00 [medline]
PHST- 2019/07/01 00:00 [pmc-release]
AID - ijms20143589 [pii]
AID - ijms-20-03589 [pii]
AID - 10.3390/ijms20143589 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jul 23;20(14):3589. doi: 10.3390/ijms20143589.