Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease.
OBJECTIVE
The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease.


METHODS
GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls.


RESULTS
The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03-2.71, p =0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89-9.97, p =0.0003).


CONCLUSIONS
The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.
Ladero
José M
JM
Services of Gastroenterology, Universidad Complutense de Madrid, Spain. jladero.hcsc@salud.madrid.org
Martínez
Carmen
C
García-Martin
Elena
E
Fernández-Arquero
Miguel
M
López-Alonso
Gustavo
G
de la Concha
Emilio Gómez
EG
Díaz-Rubio
Manuel
M
Agúndez
José A G
JA
D000328:Adult; D000368:Aged; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics*; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
D004247:DNA; D005819:Genetic Markers; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1