Elevated levels of hemoglobin-associated acetaldehyde related to alcohol drinking in the atypical genotype of low Km aldehyde dehydrogenase.
Acetaldehyde is suspected to be the ultimate carcinogen in alcohol-related carcinogenesis. The atypical genotypes of low Km aldehyde dehydrogenase (ALDH2) have higher blood concentrations of free acetaldehyde after drinking alcohol. We measured levels of acetaldehyde reversibly bound to hemoglobin (HbAA) after drinking 0.4 ml/kg ethanol using fluorigenic high performance liquid chromatography method in volunteers with the two major ALDH2 genotypes. In the ALDH2*1/*1 genotype with high ALDH2 activity, the increase of HbAA was small. By contrast, in the ALDH2*1/*2 genotype with low ALDH2 activity, HbAA increased considerably at 1-6 h after the drink, and the elevated levels persisted up to 48 h. We also measured HbAA in 81 male workers. Although HbAA levels were significantly correlated with alcohol consumption levels in both of the ALDH2 genotypes, the slope was significantly steeper in the ALDH2*1/*2 genotype than in the ALDH2*1/*1 genotype. In summary, we demonstrated for the first time a significant difference in the increase of HbAA levels after drinking alcohol, depending on the ALDH2 genotype. The HbAA levels are not only a good biomarker for increased internal exposure levels to acetaldehyde but may also be a predictive biomarker for acetaldehyde-mediated carcinogenesis.
Takeshita
T
T
Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, Suita, Japan.
Kawai
T
T
Morimoto
K
K
D000079:Acetaldehyde / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005838:Genotype; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D006454:Hemoglobins; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde