EFFECTS OF CIMETIDINE ON BLOOD ETHANOL LEVELS AFTER ALCOHOL INGESTIONAND GENETIC POLYMORPHISMS OF SIGMA-ALCOHOL DEHYDROGENASE IN JAPANESE

Administration of cimetidine, an H-2-receptor antagonist, increases bl ood alcohol concentrations. This has been attributed to decreased gast ric first-pass metabolism of ethanol caused by cimetidine's inhibitory effect on gastric alcohol dehydrogenase (sigma-ADH) activity. Molecul ar studies on sigma-ADH showed that a point mutation might occur at po sition 287 (G --> T) of the sigma-ADH gene in Japanese deficient type of sigma-ADH activity. To clarify the relationship between first-pass metabolism of ethanol and polymorphism of sigma-ADH, we analyzed the n ucleotide sequence at positions 287 and 294 of sigma-ADH in 11 individ uals who were administered ethanol orally before and after treatment w ith cimetidine. Higher blood ethanol levels after cimetidine administr ation were found in 4 of 11 cases (group A), whereas high blood ethano l levels were observed in 7 of 11 cases (B group), irrespective of cim etidine administration. Genetic polymorphisms at position 287 and 294 were not observed in all subjects. Even in 59 Japanese men with variou s alcoholic liver diseases, no polymorphisms at position 287 were obse rved by restriction-length polymorphisms with Avail digestion after po lymerase chain reaction.