Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women

Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women

CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it wit...

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Autores principales: VARELA,NELSON M, QUIÑONES,LUIS A, ORELLANA,MYRIAM, PONIACHIK,JAIME, CSENDES,ATTILA, SMOK,GLADYS, RODRIGO,RAMÓN, CÁCERES,DANTE D, VIDELA,LUIS A
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2008
Materias:
steatohepatitis
NASH
CYP2E1
obesity
genotype
chlorzoxazone
Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000100010
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spelling oai:scielo:S0716-976020080001000102008-08-21Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese WomenVARELA,NELSON MQUIÑONES,LUIS AORELLANA,MYRIAMPONIACHIK,JAIMECSENDES,ATTILASMOK,GLADYSRODRIGO,RAMÓNCÁCERES,DANTE DVIDELA,LUIS A steatohepatitis NASH CYP2E1 obesity genotype chlorzoxazone CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups: (i) normal; (ii) steatosis; and (iii) steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45%; p=0.024) and steatosis (22%; p=0.032) group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15%, p=0.027) compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026). In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicityinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.41 n.1 20082008-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000100010en10.4067/S0716-97602008000100010
institution Scielo Chile
collection Scielo Chile
language English
topic steatohepatitis
NASH
CYP2E1
obesity
genotype
chlorzoxazone
spellingShingle steatohepatitis
NASH
CYP2E1
obesity
genotype
chlorzoxazone
VARELA,NELSON M
QUIÑONES,LUIS A
ORELLANA,MYRIAM
PONIACHIK,JAIME
CSENDES,ATTILA
SMOK,GLADYS
RODRIGO,RAMÓN
CÁCERES,DANTE D
VIDELA,LUIS A
Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
description CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups: (i) normal; (ii) steatosis; and (iii) steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45%; p=0.024) and steatosis (22%; p=0.032) group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15%, p=0.027) compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026). In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicity
author VARELA,NELSON M
QUIÑONES,LUIS A
ORELLANA,MYRIAM
PONIACHIK,JAIME
CSENDES,ATTILA
SMOK,GLADYS
RODRIGO,RAMÓN
CÁCERES,DANTE D
VIDELA,LUIS A
author_facet VARELA,NELSON M
QUIÑONES,LUIS A
ORELLANA,MYRIAM
PONIACHIK,JAIME
CSENDES,ATTILA
SMOK,GLADYS
RODRIGO,RAMÓN
CÁCERES,DANTE D
VIDELA,LUIS A
author_sort VARELA,NELSON M
title Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
title_short Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
title_full Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
title_fullStr Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
title_full_unstemmed Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
title_sort study of cytochrome p450 2e1 and its allele variants in liver injury of nondiabetic, nonalcoholic steatohepatitis obese women
publisher Sociedad de Biología de Chile
publishDate 2008
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000100010
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