Contribution of the alcohol dehydrogenase-1B genotype and oral microorganisms to high salivary acetaldehyde concentrations in Japanese alcoholic men.
The less-active homozygous alcohol dehydrogenase-1B (ADH1B*1/*1) and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) increase the risk of upper aerodigestive tract cancer (UADTC) in Japanese alcoholics. We evaluated associations between ADH1B/ALDH2 genotypes and the blood and salivary ethanol/acetaldehyde levels of 80 Japanese alcoholic men in the morning when they first visited our hospital after drinking the day before. Higher levels of ethanol persisted in the blood for longer periods in ADH1B*1/*1 carriers (n = 25) than in ADH1B*2 allele carriers after adjustment for the amount and time of the preceding alcohol consumption and body weight [median (25th-75th %): 20.5 mM (15.5-52.4) vs. below detection level (<DL) (<DL-6.4), p = 0.0003]. The ethanol levels in blood and saliva were similar, but the acetaldehyde levels in saliva were strikingly higher than in the blood, and were higher in ADH1B*1/*1 carriers than in ADH1B*2 allele carriers [47.4 muM (22.2-87.6) vs. 1.60 (<DL-26.3) in the saliva, p = 0.009]. The salivary acetaldehyde levels were correlated with salivary acetaldehyde production (r = 0.34, p = 0.002). The oral bacteria and yeast counts were correlated with salivary acetaldehyde production. Both the microorganisms counts and acetaldehyde production decreased after 3 weeks of abstinence, and the decreases were correlated (r = 0.35, p = 0.042). No effect of inactive ALDH2 (n = 12) on ethanol lingering the next morning was observed. In conclusion, the high salivary acetaldehyde levels in the alcoholics were partly attributable to prolonged ethanol exposure because of the less-active ADH1B and increased salivary acetaldehyde production as a result of oral microorganism overgrowth, and may explain their high risk for UADTC.
Yokoyama
Akira
A
National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa 239-0841, Japan. a_yokoyama@kurihama1.hosp.go.jp
Tsutsumi
Eri
E
Imazeki
Hiromi
H
Suwa
Yoshihide
Y
Nakamura
Chizu
C
Yokoyama
Tetsuji
T
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000097:blood; D006801:Humans; D007564:Japan; D009055:Mouth / Q000382:microbiology*; D012463:Saliva / Q000378:metabolism*
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde