Association of polymorphism in alcohol dehydrogenase and interaction with other genetic risk factors with alcoholic liver cirrhosis.
The association of polymorphism of alcohol dehydrogenase (ADH) and its interaction with genes involved in the generation and detoxification of free radicals such as cytochrome P4502E1 (CYP2E1) and glutathione S-transferases M1 (GSTM1) were studied with alcoholic liver cirrhosis. The study included 175 alcoholic cirrhotic patients, 140 non-alcoholic cirrhotic patients, 255 non-alcoholic controls and 140 alcoholic controls. Our data revealed that the ADH1C*1/*1 genotype exhibited significant association with alcoholic liver cirrhosis while ADH1B genotypes did not show any significant association. A much higher risk to alcoholic liver cirrhosis was observed in patients carrying a combination of wild genotypes of ADH1C (ADH1C*1/*1) and variant genotype of ADH1B (ADH1B*2/*2) or CYP2E1 (CYP2E1*5B) or null genotype of GSTM1. Our data suggest a role for the interaction amongst the genes involved in metabolizing alcohol and in generating and detoxifying free radicals with susceptibility to alcoholic liver cirrhosis.
Khan
Anwar Jamal
AJ
Developmental Toxicology Division, Indian Institute of Toxicology Research (Formerly ITRC), CSIR, P.O. Box 80, M.G. Marg, Lucknow 226 001, U.P., India.
Husain
Qayyum
Q
Choudhuri
Gourdas
G
Parmar
Devendra
D
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007194:India / Q000453:epidemiology; D007527:Isoenzymes / Q000235:genetics; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D004247:DNA; D005982:Glutathione Transferase; D007527:Isoenzymes; C489332:ADH1B protein, human; C420272:ADH1C protein, human