GLUTATHIONE-S-TRANSFERASE GST M1 NULL GENOTYPE AND THE RISK OF ALCOHOLIC LIVER-DISEASE

The present study was conducted to investigate possible association be tween the occurrence of glutathione-S-transferase GST M1 ''null'' geno type and alcoholic liver disease (ALD), The ''null'' genotype indicati ng absent activity of class mu glutathione transferase was assessed in 33 abstainers, 43 moderate alcohol consumers, and 313 heavy alcohol c onsumers by polymerase chain reaction. The genotypes were compared wit h occurrence of alcoholic fatty liver, alcoholic hepatitis, and alcoho lic liver fibrosis. The ''null'' genotype was found among 44.7% of pat ients in the series, with no significant differences between different consumption groups: controls, 36.4%; moderate consumers, 39.5%; and h eavy consumers, 46.3%. Occurrence of GST M1 ''null'' genotype was not associated with occurrence ALD among moderate alcohol consumers, Frequ ency of the ''null'' genotype was, however, statistically nearly signi ficantly [p = 0.07, odds ratio (OR) = 1.75] lower among heavy consumer s with normal liver histology than in alcoholics with ALD. Furthermore , when compared with heavy consumers without ALD, the ''null'' genotyp e was nearly significantly more frequent among heavy consumers with at least slight liver fibrosis (p = 0.05, OR = 1.8) and statistically si gnificantly more frequent among alcoholics with advanced liver fibrosi s (p < 0.025, OR = 2.3), Results of the present Finnish association st udy suggest that homozygous deletion of the GST M1 gene may indicate i ncreased susceptibility to develop irreversible liver damage in respon se to the toxic effects of ethanol. Significant association was found between the occurrence of the ''null'' genotype and the occurrence of alcoholic liver cirrhosis.