CYP2E1: from ASH to NASH

Lieber, Charles S.

doi:10.1016/j.hepres.2003.08.001

Cited by 142 publications

(91 citation statements)

References 122 publications

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“…These genetic and environmental factors may explain the good lipid levels observed in HUI and may protect them of liver dysfunction in spite of the well-known ancestral high consumption of alcohol among indigenous groups as part of their way of life (Bruman, 2000) and the unusual high frequency of the CYP2E1*c2 allele observed. Nevertheless, well designed case-control studies to elucidate the role of this polymorphic allele in pathologies where oxidative stress constitute critical factors, like ALD (Lu and Cederbaum, 2008), nonalcoholic steatohepatitis (Lieber, 2004a), obesity and diabetes (Lieber, 2004b), should be accomplished in HUI.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1c2* Allele

Gordillo-Bastidas

Panduro

Gordillo-Bastidas

et al. 2009

Alcoholism Clin & Exp Res

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Background: Alcohol abuse represents the major identified etiological factor of cirrhosis in Me´xico. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out.Methods: One hundred and one HUI and 331 MES subjects were studied. Genotype and allele frequency were assessed through polymerase chain reaction-restriction fragment length polymorphism after DNA isolation from peripheral leukocytes. Commercial kits for lipid and hepatic determinations were used.Results: Polymorphic allele distribution in HUI was: 0% ADH1B*2, 0.5% ALDH2*2, 51.5% CYP2E1*c2; in MES: 3.4% ADH1B*2, 0% ALDH2*2, 16.1% CYP2E1*c2. Frequency of ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2 polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic profile was normal in both groups. HUI showed a better lipid profile than MES independently of genotype.Conclusions: Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary. The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype. This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1c2* Allele

Gordillo-Bastidas

Panduro

Gordillo-Bastidas

et al. 2009

Alcoholism Clin & Exp Res

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“…A detailed discussion of each of these putative factors is beyond the scope of this paper and is available in recent reviews [4,[20][21][22]. It is important to note here, however, that these mechanisms are not mutually exclusive; but instead, likely act in a coordinated and cooperative manner to hasten the development and progression of NASH.…”

Section: Two-hit Hypothesismentioning

confidence: 98%

“…Several factors have been suggested to constitute the second hit(s), most notably oxidative stress, pro-inflammatory cytokines and gut-derived bacterial endotoxin [4,[20][21][22]. A detailed discussion of each of these putative factors is beyond the scope of this paper and is available in recent reviews [4,[20][21][22].…”

Section: Two-hit Hypothesismentioning

confidence: 99%

The role of fatty acids in the development and progression of nonalcoholic fatty liver disease

Gentile

Pagliassotti

2008

The Journal of Nutritional Biochemistry

200

156

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“…Increased lipid peroxidation was demonstrated in both animal models of fatty liver [110][111][112] and patients with nonalcoholic fatty liver diseases (NAFLD) [113][114][115][116][117]. NASH patients have increased levels of oxidative stress as compared with patients with steatosis alone [113,115].…”

Section: Lipid Peroxidationmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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CYP2E1: from ASH to NASH

Cited by 142 publications

References 122 publications

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1c2* Allele

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1c2* Allele

The role of fatty acids in the development and progression of nonalcoholic fatty liver disease

Role of free radicals in liver diseases

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CYP2E1: from ASH to NASH

Cited by 142 publications

References 122 publications

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1*c2 Allele

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1*c2 Allele

The role of fatty acids in the development and progression of nonalcoholic fatty liver disease

Role of free radicals in liver diseases

Contact Info

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Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1c2* Allele

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1c2* Allele