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

World Journal of Gastroenterology 2005年第41期11卷 6445-6449页

作者： 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 Department of Surgery Derriford Hospital Plymouth United Kingdom Department of Gastroenterology Derriford Hospital Plymouth United Kingdom Department of Molecular Medicine Plymouth Postgraduate Medical School Plymouth United Kingdom Department of Surgery University of Magdeburg Magdeburg Germany Outpatient Clinic for Addiction Diseases Magdeburg Germany

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 ***: 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 endorgan 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 ***: 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.

关键词： CYP2E1 Alcohol Chronic pancreatitis Liver disease Polymorphism

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