In those homozygous for ALDH2*1, the presence of two ADH2*2 alleles correlated with slightly faster alcohol metabolism and more intense flushing, although a great deal of variability in the latter was noted.
In addition, among the ALDH2-deficient individuals, the atypical homozygote was obviously more hypersensitive to alcohol than the heterozygote, judging from the frequency of flushing or other drinking-associated manifestations with a small dose of alcohol.
The flushing reaction is observed mainly in individuals who possess a mutation in the high-affinity aldehyde dehydrogenase (ALDH2) which renders the enzyme inactive.
These preliminary results indicate that variability in the facial flushing reaction to alcohol seems to be a phenomenon resulting not only from the presence of a deficient ALDH2*2 allele, but also from other polymorphisms of alcohol-metabolizing enzymes.
In the ALDH2(1)/ALDH2(2) group, the frequency of facial flushing with one glass of beer was significantly higher in the ADH2(1)/ADH2(2) and ADH2(2)/ADH2(2) genotype than in the ADH2(1)/ADH2(1) genotype.
The mutation in the mitochondrial aldehyde dehydrogenase (ALDH2) gene responsible for alcohol-induced flushing increases turnover of the enzyme tetramers in a dominant fashion.
The first examination of 53 normal volunteers showed that there were differences in the degree of alcohol flushing between the ALDH2 genotypes (P < 0.01).
The results suggest the utility of this simple flushing questionnaire in daily practice, as well as large-scale studies to assess cancer risks associated with drinking and ALDH2 and for activities aimed at preventing alcohol-related cancer.
The results indicate that self-reported flushing is determined by both ALDH2 and ADH2 and that prediction of ALDH2 genotype on the basis of self-reported flushing and nausea can help identify subjects at increased risk for alcoholism.
The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable screening procedure for the highest risk gene combination (ADH2*1/2*1 and ALDH2*1/2*2) will require further investigation.
From 60 to 120 min, the non-flushing group which had homozygous ALDH2* 1 (active type) displayed significant increase not only in the alpha power but also in the interval dipolarity compared to the baseline, whereas the flushing group with heterozygous ALDH2*1/2*2 (inactive type) did not exhibit this significant increase.
The flushing questionnaire may be used in large-scale epidemiological studies as a surrogate marker of ALDH2 genotype to predict individual cancer risk.
The drinking behavior, alcohol-induced facial flushing and ALDH2 genotypes were determined in 283 Thai men comprising 85 who were alcohol-dependent, 62 hazardous/harmful drinkers and 136 non-drinkers or infrequent drinkers.
The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype.
Japanese alcoholic men with (n = 65) and without (n = 206) esophageal squamous cell carcinomas, excluding those with liver cirrhosis, were assessed for MCV within 7 days of their last drink, alone or in combination with findings from either the alcohol flushing questionnaire or genotyping to identify inactive aldehyde dehydrogenase-2 (ALDH2*1/2*2) and the less-active form of alcohol dehydrogenase-2 (ADH2*1/2*1), which pose risks for esophageal squamous cell carcinoma.
The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks.
Specifically, ADH1B*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption.
Mr. Cook's and Dr. Wall's paper adds another dimension to this article by presenting research on both the aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH2) genetic variants and their association with the alcohol-related flushing response that is prevalent in Asian populations.
The immuno-staining of ALDH2 in the esophageal epithelium was compared with both the drinking habit and the occurrence of flushing that is closely associated with the ALDH2 deficiency.
The replies to a questionnaire about facial flushing in response to alcohol showed that the trend was more prominent in men with current/former flushing, a surrogate marker for inactive ALDH2, than in men with no flushing (p < 0.0001).
The results obtained using an alcohol-flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping [adjusted ORs (95% CIs) per +7 U/wk increment of alcohol drinking were 3.94 (1.87-8.31) and 1.46 (0.96-2.23) in those with and without flushing, respectively; p = 0.021 for difference in OR].
Individuals who carry a low-activity ALDH2 (ALDH2*2) display high blood acetaldehyde levels after ethanol consumption, which leads to dysphoric effects, such as facial flushing, nausea, dizziness, and headache ("Asian alcohol phenotype"), which result in an aversion to alcohol and protection against alcohol abuse and alcoholism.