Literature DB >> 16425414

Cytochrome P450 2E1 high activity polymorphism in alcohol abuse and end-organ disease.

Mark T Cartmell1, Hans-Ulrich Schulz, Derek A O'Reilly, Bing-Mei Yang, Volker Kielstein, Simon P Dunlop, Walter Halangk, Andrew G Demaine, Andrew N Kingsnorth.   

Abstract

AIM: To investigate a possible role for a recently identified polymorphism in the gene of cytochrome P450 2E1, the presence of which is associated with high activity of the enzyme.
METHODS: Two hundred and thirty-nine alcohol consumers, ICD 10.1/.2 (ALC), and 208 normal controls were studied. PCR amplification of the CYP2E1 gene region was performed to assess polymorphic variation. Fisher's exact test was used to assess the data.
RESULTS: Twelve normal controls (5.8%) possessed the insertion. Five ALC (2.1%) had the insertion; of these 2 of 144 with alcohol induced chronic pancreatitis, none of 28 with alcoholic liver disease and 3 of 67 without end-organ disease had the polymorphism. A significantly Lower frequency of subjects possessed the insertion than normal controls [P=0.049 (genotype analysis P=0.03)]. To further assess, if there was a relationship to alcohol problems per se or end-organ disease, we compared patients with alcohol induced end-organ disease vs alcoholic controls without end-organ disease vs normal controls which again showed a significant difference [P=0.045 (genotype analysis, P=0.011)], further sub-group analysis did not identify which group(s) accounted for these differences.
CONCLUSION: We have shown the frequencies of this high-activity polymorphism in alcohol related patient groups for the first time. The frequency is significantly less in alcoholics than normal controls, as with high activity polymorphisms of alcohol dehydrogenase. The biological significance, and whether the relevance is solely for alcoholism or is there a relationship to end-organ disease, would benefit from the assessment in the populations with a greater frequency of this polymorphism.

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Year:  2005        PMID: 16425414      PMCID: PMC4355784          DOI: 10.3748/wjg.v11.i41.6445

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


  33 in total

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2.  Inducibility of cytochromes P-4502E1 and P-4501A1 in the rat pancreas.

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3.  Polymorphism of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men.

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6.  Structural and functional characterization of the 5'-flanking region of the rat and human cytochrome P450 2E1 genes: identification of a polymorphic repeat in the human gene.

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7.  The RsaI polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians: effect on age of presentation and dependence on alcohol dehydrogenase genotype.

Authors:  J Grove; A S Brown; A K Daly; M F Bassendine; O F James; C P Day
Journal:  Pharmacogenetics       Date:  1998-08

8.  Mutations in the exons and exon-intron junction regions of human cytochrome P-4502E1 gene and alcoholism.

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9.  Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA.

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10.  Relationship between alcoholism and CYP2E1 C/D polymorphism.

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