Accumulation of hemoglobin-associated acetaldehyde with habitual alcohol drinking in the atypical ALDH2 genotype.
BACKGROUND
Those with the atypical genotypes of low Km aldehyde dehydrogenase (ALDH2) have high blood concentrations of free acetaldehyde, an active metabolite of ethanol, after drinking alcohol. In the present study, we measured acetaldehyde reversibly bound to hemoglobin (HbAA) in Japanese male workers.


METHODS
One hundred and sixty Japanese male workers in one plant participated with informed consent. The subjects were genotyped for the ALDH2 polymorphism by polymerase chain reaction method. HbAA levels were measured using a high performance liquid chromatography system with a fluorescence detector. For the study in which we examined accumulation of HbAA, eight Asian male volunteers participated with informed consent.


RESULTS
Although HbAA levels were significantly correlated with recent alcohol consumption in both typical (ALDH2*1/*1) and atypical (ALDH2*1/*2) genotypes, the slope in ALDH2*1/*2 was significantly steeper than that in ALDH2*1/*1. Multiple regression analysis on relevant factors for HbAA revealed that not only recent but also daily alcohol consumption increased HbAA levels in those with the ALDH2*1/*2 genotype, which suggests that HbAA accumulates with habitual drinking. We measured HbAA levels before, during, and after alcohol consumption--one drink (0.4 ml/kg) per day--for 7 consecutive days in male volunteers. During the drinking period, HbAA linearly increased in ALDH2*1/*2 (n = 4) but not in ALDH2*1/*1 (n = 4). After reaching peak levels (+76.1 nmol/g hemoglobin) following the seventh drink, HbAA levels gradually decreased but were significantly higher for 3 days after drinking was discontinued.


CONCLUSIONS
We demonstrated that HbAA levels accumulate with habitual alcohol drinking in the atypical ALDH2 genotype. HbAA was shown to be a good biomarker for increased internal exposure levels to acetaldehyde.
Takeshita
T
T
Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Morimoto
K
K
D000079:Acetaldehyde / Q000097:blood*; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005838:Genotype; D006441:Hemoglobin A / Q000378:metabolism*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012907:Smoking / Q000097:blood
D006441:Hemoglobin A; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde