Ethanol is almost completely metabolized by oxidative metabolism in humans. Alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (CYP2E1) are the primary enzymes that catalyze the conversion of ethanol to acetaldehyde and then to acetate. Genetic polymorphisms have been reported in the ADH2, ADH3, and ALDH2 loci and in the 5'-flanking region of CYP2E1 [1]. Such polymorphisms might play a role in an individual's susceptibility to alcoholic liver disease [2]. The aim of our study was to determine whether genetic polymorphism influences the severity of alcoholic liver disease in Italian patients.

One hundred persons with chronic alcoholism (defined as consumption of >150 g of ethanol per day for more than 10 years) were studied. Of these 100 persons, 65 were men; the mean age (±SD) was 45 ± 10 years. Twenty-six had fatty liver, 26 had nonspecific changes, 29 had steatofibrosis, and 19 had liver cirrhosis. Restriction fragment length polymorphisms in the ADH2, ADH3, ALDH2, and CYP2E1 genes were detected by digestion of polymerase chain reaction-amplified DNA [3-5]. One patient was an ADH2*1/*2 heterozygote; all of the others were ADH2*1/*1 homozygotes. All of the patients were ALDH2*1/*1 homozygotes. The CYP2E1 genotype B (heterozygote c1/c2) was present in only 5 patients; the others were all c1/c1 homozygotes (type A). The ADH3 gene showed the following distribution: ADH3*1/*1 in 54 patients ADH3*1/*2 in 36 patients, and ADH3*2/*2 in 10 patients. None of the genotypes studied correlated statistically with the severity of liver disease. In particular, patients with extensive liver fibrosis (on liver morphometry) or cirrhosis (n = 42) did not show a characteristic genotype, in contrast with patients who had fatty liver or nonspecific changes. Moreover, neither the liver enzyme messenger RNA expression (evaluated by Northern blotting) nor the expression of enzymatic activity or protein in liver tissues correlated with the degree of alcohol-induced hepatic injury.

In conclusion, our results suggest that genetic polymorphisms and liver phenotypes of ADH2, ADH3, ALDH2, and CYP2E1 do not influence the severity of alcoholic liver disease in Italian patients.