Genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease and hepatocellular carcinoma in a white population: a studyand literature review, including meta-analysis

Aims-To investigate the associations between the Rsa I, Dra I, and Tag I ge netic polymorphisms of cytochrome p4502EI and susceptibility to alcoholic l iver disease or to hepatocellular carcinoma, Methods-DNA samples isolated from 61 patients with alcoholic liver disease, 46 patients with hepatocellular carcinoma, and 375 healthy controls were s ubjected to polymerase chain reaction amplification followed by digestion w ith the endonucleases Rsa I, Dra I, or Tao I. Meta-analysis was performed u sing data from previous studies of Rsa I polymorphism and the risk of alcoh olic liver disease. Results-No association was found between any of the three polymorphisms and susceptibility to hepatocellular carcinoma. The distributions of Rsa I and Dra I alleles among the patients with alcoholic liver disease were not sig nificantly different from those among the control group. Meta-analysis of t his data and previous data concerning Rsa I polymorphism and alcoholic live r disease risk failed to demonstrate any significant association between th e two. However, the alcoholic liver disease group in this study showed a si gnificantly lower frequency of the less common Tag I allele compared with t he healthy control group (odds ratio, 0.33; 95% confidence interval, 0.12 t o 0.78). Conclusions-Possession of the less common Tag I cytochrome p4502E1 allele i s associated with reduced susceptibility to alcoholic liver disease. There is no existing evidence that the Tao I polymorphism is directly associated with altered alcohol metabolism, but it might be in linkage disequilibrium with as yet unidentified protective factors.