Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2005; 11(41): 6445-6449
Published online Nov 7, 2005. doi: 10.3748/wjg.v11.i41.6445
Cytochrome P450 2E1 high activity polymorphism in alcohol abuse and end-organ disease
Mark T Cartmell, Hans-Ulrich Schulz, Derek A O’Reilly, Bing-Mei Yang, Volker Kielstein, Simon P Dunlop, Walter Halangk, Andrew G Demaine, Andrew N Kingsnorth
Mark T Cartmell, Derek A O’Reilly, Andrew N Kingsnorth, Department of Surgery, Derriford Hospital, Plymouth, United Kingdom
Simon P Dunlop, Department of Gastroenterology, Derriford Hospital, Plymouth, United Kingdom
Bing-Mei Yang, Andrew G Demaine, Department of Molecular Medicine, Plymouth Postgraduate Medical School, Plymouth, United Kingdom
Hans-Ulrich Schulz, Walter Halangk, Department of Surgery, University of Magdeburg, Magdeburg, Germany
Volker Kielstein, Outpatient Clinic for Addiction Diseases, Magdeburg, Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Mr Mark T Cartmell, c/o Professor Kingsnorth, Derriford Hospital, Plymouth PL6 8DH, United Kingdom. markcartmell@hotmail.com
Telephone: +44-1752-763017 Fax: +44-1752-763007
Received: March 4, 2005
Revised: April 1, 2005
Accepted: April 2, 2005
Published online: November 7, 2005
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.

Keywords: CYP2E1; Alcohol; Chronic pancreatitis; Liver disease; Polymorphism