title: Association of polymorphism in alcohol dehydrogenase and interaction with other genetic risk factors with alcoholic liver cirrhosis.
abstract: 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.
authors.affiliation: Developmental Toxicology Division, Indian Institute of Toxicology Research (Formerly ITRC), CSIR, P.O. Box 80, M.G. Marg, Lucknow 226 001, U.P., India.
authors.forename: Anwar Jamal
authors.initials: AJ
authors.lastname: Khan
authors.forename: Qayyum
authors.initials: Q
authors.lastname: Husain
authors.forename: Gourdas
authors.initials: G
authors.lastname: Choudhuri
authors.forename: Devendra
authors.initials: D
authors.lastname: Parmar
mesh_terms: 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
chemical_list: D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D004247:DNA; D005982:Glutathione Transferase; D007527:Isoenzymes; C489332:ADH1B protein, human; C420272:ADH1C protein, human