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.