Glutathione-S-transferase GST M1 "null" genotype and the risk of alcoholic liver disease.
The present study was conducted to investigate possible association between the occurrence of glutathione-S-transferase GST M1 "null" genotype and alcoholic liver disease (ALD). The"null" genotype indicating absent activity of class mu glutathione transferase was assessed in 33 abstainers, 43 moderate alcohol consumers, and 313 heavy alcohol consumers by polymerase chain reaction. The genotypes were compared with occurrence of alcoholic fatty liver, alcoholic hepatitis, and alcoholic liver fibrosis. The "null" genotype was found among 44.7% of patients in the series, with no significant differences between different consumption groups: controls, 36.4%; moderate consumers, 39.5%; and heavy consumers, 46.3%. Occurrence of GST M1 "null" genotype was not associated with occurrence ALD among moderate alcohol consumers. Frequency of the "null" genotype was, however, statistically nearly significantly [p = 0.07, odds ratio (OR) = 1.75] lower among heavy consumers with normal liver histology than in alcoholics with ALD. Furthermore, when compared with heavy consumers without ALD, the "null" genotype was nearly significantly more frequent among heavy consumers with at least slight liver fibrosis (p = 0.05, OR = 1.8) and statistically significantly more frequent among among alcoholics with advanced liver fibrosis (p < 0.025, OR = 2.3). Results of the present Finnish association study suggest that homozygous deletion of the GST M1 gene may indicate increased susceptibility to develop irreversible liver damage in response to the toxic effects of ethanol. Significant association was found between the occurrence of the "null" genotype and the occurrence of alcoholic liver cirrhosis.
Savolainen
V T
VT
Department of Forensic Medicine, University of Helsinki, Finland.
Pjarinen
J
J
Perola
M
M
Penttilä
A
A
Karhunen
P J
PJ
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012307:Risk Factors
D005982:Glutathione Transferase