Polymorphisms of the gene for microsomal epoxide hydrolase and susceptibility to alcoholic liver disease and hepatocellular carcinoma in a Caucasian population

The gene encoding the xenobiotic-metabolising microsomal enzyme, epoxide hy drolase (mEPHX), shows two common mutations, i.e. at exons 3 and 4. It is u nknown how these genetic polymorphisms relate to risk of developing alcohol ic liver disease (ALD) and/or hepatocellular carcinoma (HCC) in a Caucasian population. DNA samples extracted from the blood of 61 ALD patients and 20 3 healthy controls, and from archival liver tissue of 46 cases of HCC, were subjected to polymerase chain reaction amplification followed by digestion with EcoR V or Rsa I to demonstrate polymorphisms of exon 3 or 4, respecti vely. The distributions of the genotypes of exon 3 in the ALD and HCC patie nts, and exon 4 in the HCC patients did not differ significantly from those of the control group. However, compared with the control group, the ALD gr oup contained a significantly greater number of individuals homozygous or h eterozygous for the exon 4 mutation. This suggested association between pos session of the exon 4 mutant mEPHX allele and increased risk of developing ALD may relate to known interactions between mEPHX and alcohol-metabolising enzyme systems, or to linkage disequilibrium between the mutation and othe r genetic risk factors for ALD. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.