Alcohol sensitivity in Taiwanese men with different alcohol and aldehyde dehydrogenase genotypes.
OBJECTIVE
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.


CONCLUSIONS
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.
Peng
Giia-Sheun
GS
Department of Neurology, Tri-Service General Hospital, Taipei, Taiwan.
Yin
Jiu-Haw
JH
Wang
Ming-Fang
MF
Lee
Jiuun-Tay
JT
Hsu
Yaw-Don
YD
Yin
Shih-Jiun
SJ
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D001783:Blood Flow Velocity / Q000502:physiology; D002492:Central Nervous System Depressants / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D005145:Face / Q000098:blood supply; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D013624:Taiwan / Q000208:ethnology
D002492:Central Nervous System Depressants; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase