BACKGROUND AND PURPOSE: Previous studies demonstrated that ADH2*2, encoding for high-maximal velocity (Vmax) beta2-alcohol dehydrogenase (ADH) activity, and mutant ALDH2*2, encoding for null aldehyde dehydrogenase (ALDH) 2 activity, independently influence susceptibility to alcoholism. A single copy of the ALDH2*2 allele may protect less strongly than a single copy of ADH2*2 in individuals carrying only one copy of either ALDH2*2 or ADH2*2. Individuals with various ADH2 and ALDH2 gene status may exhibit different alcohol metabolism and alcohol sensitivity, which affects drinking behavior. To explore the underlying pharmacogenetic mechanism, alcohol metabolism and alcohol sensitivity were tested using ethanol challenge in Taiwanese men with different ADH2 and ALDH2 genotypes. METHODS: Twenty-four adults, matched by age, body mass index, nutritional state, and homozygosity at ADH3, were recruited from a population base of 304 men. Six individuals were chosen with each of the different ADH2 and ALDH2 genotypes: ADH2*1/*1, ALDH2*1/*1; ADH2*2/*2, ALDH2*1/*1; ADH2*1/*1, ALDH2*1/*2; and ADH2*2/*2, ALDH2*1/*2. After a low-to-moderate challenge with ethanol (0.3 g/kg), blood ethanol and acetaldehyde concentrations, heart rate, and facial capillary blood flow (FCBF) were measured for 130 minutes. RESULTS: All heterozygous ALDH2*2 individuals were found to be strongly responsive to low-to-moderate ethanol, as evidenced by pronounced increases in heart rate and FCBF. Conversely, there were no significant differences in alcohol metabolism and alcohol sensitivity between the ADH2*2 and ADH2*1 homozygotes with identical ALDH2 genotype. CONCLUSION: Individuals heterozygous for ALDH2*2 exhibit strong alcohol hypersensitivity caused by persistent accumulation of large amounts of acetaldehyde, but homozygosity for ADH2*2 is not dependent upon this pathway against alcoholism.
BACKGROUND AND PURPOSE: Previous studies demonstrated that ADH2*2, encoding for high-maximal velocity (Vmax) beta2-alcohol dehydrogenase (ADH) activity, and mutant ALDH2*2, encoding for null aldehyde dehydrogenase (ALDH) 2 activity, independently influence susceptibility to alcoholism. A single copy of the ALDH2*2 allele may protect less strongly than a single copy of ADH2*2 in individuals carrying only one copy of either ALDH2*2 or ADH2*2. Individuals with various ADH2 and ALDH2 gene status may exhibit different alcohol metabolism and alcohol sensitivity, which affects drinking behavior. To explore the underlying pharmacogenetic mechanism, alcohol metabolism and alcohol sensitivity were tested using ethanol challenge in Taiwanese men with different ADH2 and ALDH2 genotypes. METHODS: Twenty-four adults, matched by age, body mass index, nutritional state, and homozygosity at ADH3, were recruited from a population base of 304 men. Six individuals were chosen with each of the different ADH2 and ALDH2 genotypes: ADH2*1/*1, ALDH2*1/*1; ADH2*2/*2, ALDH2*1/*1; ADH2*1/*1, ALDH2*1/*2; and ADH2*2/*2, ALDH2*1/*2. After a low-to-moderate challenge with ethanol (0.3 g/kg), blood ethanol and acetaldehyde concentrations, heart rate, and facial capillary blood flow (FCBF) were measured for 130 minutes. RESULTS: All heterozygous ALDH2*2 individuals were found to be strongly responsive to low-to-moderate ethanol, as evidenced by pronounced increases in heart rate and FCBF. Conversely, there were no significant differences in alcohol metabolism and alcohol sensitivity between the ADH2*2 and ADH2*1 homozygotes with identical ALDH2 genotype. CONCLUSION: Individuals heterozygous for ALDH2*2 exhibit strong alcoholhypersensitivity caused by persistent accumulation of large amounts of acetaldehyde, but homozygosity for ADH2*2 is not dependent upon this pathway against alcoholism.
Authors: Susan E Luczak; Danielle Pandika; Shoshana H Shea; Mimy Y Eng; Tiebing Liang; Tamara L Wall Journal: Alcohol Clin Exp Res Date: 2011-02-28 Impact factor: 3.455
Authors: Christian S Hendershot; Susan E Collins; William H George; Tamara L Wall; Denis M McCarthy; Tiebing Liang; Mary E Larimer Journal: Alcohol Clin Exp Res Date: 2009-03-06 Impact factor: 3.455
Authors: Nicole C E Duranceaux; Marc A Schuckit; Susan E Luczak; Mimy Y Eng; Lucinda G Carr; Tamara L Wall Journal: J Stud Alcohol Drugs Date: 2008-03 Impact factor: 2.582