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PubMed1998

Correlation between alcohol-induced asthma and acetaldehyde dehydrogenase-2 genotype.

BACKGROUND: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due to differences in alcohol metabolism, particularly acetaldehyde metabolism. We investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2) gene on the response to alcohol challenge testing in a group of Japanese asthmatic subjects and normal subjects. METHODS: Subjects were 32 asthmatic subjects and 30 healthy individuals. We measured the change in FEV1 after ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine concentrations were determined. ALDH2 gene type was established by polymerase chain reaction. RESULTS: Ethanol provocation test results were positive in 15 (47% responders) asthmatic subjects. The blood ethanol concentration was similar in responders and nonresponders. The fall in FEV1 was associated with a rise in blood acetaldehyde and histamine concentrations. The response to oral ethanol challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2 genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%) of two patients with type mutant homozygote ALDH2 genotype. CONCLUSIONS: Alcohol-induced asthma is probably caused by increased blood acetaldehyde concentration resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype differences.

Acetaldehyde↗
PubMed2004

Assessment of association between mitochondrial aldehyde dehydrogenase polymorphism and Alzheimer's disease in an older Korean population.

BACKGROUND: The mutant allele of mitochondrial aldehyde dehydrogenase (ALDH2(*)2) was found to be associated with Alzheimer's disease (AD) in a Japanese sample, interacting with the apolipoprotein E epsilon 4 allele (Apo E4). OBJECTIVE: In a community Korean population we sought to investigate associations between ALDH2 genotypes and the following outcomes: cognitive impairment, previous cognitive decline, dementia and AD. METHODS: Six hundred ninety community residents aged 65 or over were assessed for demographic characteristics, drinking behaviour, cognitive function, clinical diagnoses of dementia and AD, physical health status, and genotype (ALDH2 and Apo E). RESULTS: There were no significant associations between the ALDH2(*)2 and any cognitive outcome, before or after adjustment for alcohol-related characteristics. These findings were consistent both in the non-drinkers and drinkers. Interaction between ALDH2 and Apo E was only found for one outcome (previous cognitive decline) at borderline levels of significance (P=0.058). CONCLUSIONS: Overall, these findings in a community population did not support a substantial role for ALDH2 genotype in the aetiology of dementia.

Acetaldehyde↗
PubMed1997

Inhibition of recombinant human mitochondrial and cytosolic aldehyde dehydrogenases by two candidates for the active metabolites of disulfiram.

We expressed recombinant human cytosolic (ALDH1, high Km) and mitochondrial aldehyde dehydrogenase (ALDH2, low Km) in Escherichia coli and purified the enzymes to homogeneity to examine the nature of inhibition of human ALDH by disulfiram, its confirmed metabolite S-methyl N,N-diethylthiocarbamate (MeDTC) sulfoxide, and its proposed metabolite MeDTC sulfone. Disulfiram, MeDTC sulfoxide, and MeDTC sulfone, respectively, were potent inhibitors with IC50 values of 0.15 +/- 0.02 microM, 0.27 +/- 0.04 microM, and 0.12 +/- 0.02 microM for ALDH1, and 1.45 +/- 0.40 microM, 1.16 +/- 0.56, and 0.40 +/- 0.10 microM for ALDH2. Extensive dialysis did not restore the activity of the inactivated enzyme, indicating irreversible inhibition. Both the esterase and dehydrogenase activities of ALDH2 were inhibited to the same extent by MeDTC sulfone and sulfoxide, suggesting that both catalytic sites are closely linked. The time course of inhibition of ALDH appeared to be first-order for both MeDTC sulfone and MeDTC sulfoxide. Kitz and Wilson plots of the half-life of inactivation versus 1/[inhibitor] indicated that the reactions between ALDH and inhibitors were bimolecular. The pseudobimolecular rate constants (k3/KI) for the ALDH-inhibitor reactions were 1 x 10(5), 1 x 10(4), 3 x 10(3), and 1 x 10(3) s-1 M-1 ALDH1-sulfone, ALDH1-sulfoxide, ALDH2-sulfone, and ALDH2-sulfoxide, respectively. ALDH2 was not significantly protected from inactivation from either MeDTC sulfoxide or MeDTC sulfone by NAD alone, but high concentrations of NAD and acetaldehyde completely prevented inhibition. Since disulfiram is rapidly metabolized in vivo, it is believed that disulfiram is too short-lived to inhibit ALDH directly. The results of our study indicate that MeDTC sulfoxide and sulfone are potent inhibitors of human ALDH and are reasonable candidates for the proximal inhibitors of ALDH following disulfiram administration.

Aldehyde Dehydrogenase↗
PubMed1995

Inhibition of gene expression by triple helix formation in hepatoma cells.

The aim of this study was to selectively inhibit human mitochondrial aldehyde dehydrogenase (ALDH2) gene expression by triple helix assembly. Eight 21-mer oligodeoxyribonucleotides were designed to bind to two purine-rich sequences in the 5'-flanking region of the human ALDH2 gene. Gel mobility shift assays showed that triplex formation is sequence-specific for the target duplex and the third strand oligonucleotide. In the presence of Mg2+, but absence of K+, triplex-forming oligonucleotides bind to their target sites with apparent dissociation constants (Kd) in the 10(-7) to 10(-9) M range. Potassium cation virtually suppressed the triplex formation of G-C-rich duplex DNA with natural oligonucleotides, but did not prevent triplex formation with phosphorothioate-modified oligonucleotides. Phosphorothioate-modified oligonucleotides were delivered into human hepatoma Hep G2 cells by cationic liposomes. The reduction in ALDH2 mRNA levels in the cells was determined by the competitive reverse transcription-polymerase chain reaction. One of the phosphorothioate-modified oligonucleotides designed to forma an antiparallel triplex with a target in the 5'-flanking region of human ALDH2 gene (-105 to -125 from the translation initiation codon ATG) reduced by 80-90% the ALDH2 mRNA levels without affecting albumin mRNA levels. Data suggest that triple-helix formation may provide a means to selectively inhibit hepatic ALDH2 gene expression for therapeutic use.

Aldehyde Dehydrogenase↗
PubMed1998

Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics.

Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2*2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 *2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers.

Adult↗
PubMed2005

Genetic associations of alcohol and aldehyde dehydrogenase with alcohol dependence and their mechanisms of action.

Two alcohol dehydrogenase genes (ADHIB and ADH1C on chromosome 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional polymorphisms that are associated with lower rates of alcohol dependence. The ALDH2*2 allele,found almost exclusively in Asian populations, has the strongest relationship. The ADH1B*2, ADH1B*3, and ADHlC*i alleles, found in varying prevalence in different ethnic groups, have also been associated with lower rates of alcohol dependence. Studies of the ADHIBand ADH1C haplotypes, however, have shown that ADH1C*I is in linkage disequilibrium with ADHiB*2, and the ADH1C*i allele does not appear to have significant unique associations with alcohol dependence. The hypothesized mechanism underlying the associations of the ADH1B and ALDH2 polymorphisms with alcohol dependence is that the isoenzymes encoded by these alleles lead to an accumulation of acetaldehyde during alcohol metabolism. Based on their kinetic properties, ALDH2 *2 theoretically should lead to a slower removal of acetaldehyde than ALDH2*1, whereas ADH1B*2 and ADH1B*3 should lead to a more rapid production of acetaldehyde than ADHIB*I. It is further hypothesized that elevations in acetaldehyde cause more intense reactions to alcohol and lead to lower levels of alcohol intake. Data are consistent with the hypothesis that elevations in acetaldehyde, increased sensitivity to alcohol, and lower levels of drinking reflect the mechanism by which the ALDH2*2 allele reduces risk for alcohol dependence. There is also some evidence supporting this mechanism for the ADH1B*2 and ADHIB*3 alleles, but the results are less consistent. These findings highlight the value of trying to elucidate the mechanism by which genes ultimately give rise to differences in alcohol dependence through the examination of mediating behaviors.

Acetaldehyde↗
PubMed1999

Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.

A case-control study was conducted to explore the possible etiologic role of alcohol and aldehyde dehydrogenase 2 (ALDH2) gene among Japanese colorectal cancer patients. Information on their drinking, smoking and dietary habits was collected from 265 colon and 164 rectum cancer patients, and 794 non-cancer patients as a control group. Genotypes of the ALDH2 gene at codon 487, glutamic acid (ALDH2*1) as a wild-type or lysine (ALDH2*2) as a mutated type with reduced enzyme activity, were analyzed by polymerase chain reaction in 160 colon and 110 rectum cancer patients and 121 control persons. Univariate analysis with the chi 2 statistical test showed that heavy alcohol drinking (P < 0.01), frequent meat intake (P < 0.001), and irregular (P < 0.01), hasty (P < 0.01) and excessive (P < 0.001) eating habits were associated with the incidence of both colon and rectum cancers, whereas heavier smoking (P < 0.05) and infrequent fish (P < 0.03) and fruit (P < 0.01) intake were solely associated with incidence of rectum cancer. Infrequent green vegetable intake was not correlated with the incidence of colorectal cancer. Multivariate unconditional logistic regression analysis confirmed the association of alcohol consumption (P < 0.01) and meat intake (P < 0.05). Homozygous and heterozygous carriers of ALDH2*2 allele tended to be found in colon (trend P = 0.04) but not in rectum cancer patients compared to controls. Risk elevation for colon cancer due to alcohol consumption was pronounced among the heterozygotes and it was statistically significant especially for distal colon cancer (trend P = 0.02). We conclude that alcohol consumption is a risk factor for colorectal cancer and the risk can be enhanced in ALDH2 heterozygotes.

Adult↗
PubMed1998

Development of a questionnaire method to discriminate between typical and atypical genotypes of low Km aldehyde dehydrogenase in a Japanese population.

Nearly half of all Orientals exhibit aversive symptoms, such as "Oriental flushing" or palpitation, during alcohol consumption. This high alcohol sensitivity among Orientals has been attributed to a highly prevalent polymorphism in low Km aldehyde dehydrogenase (ALDH2). In the present study, we attempted to develop a reliable questionnaire method to probe the frequency of alcohol drinking-related symptoms to estimate the ALDH2 genotype. Four-hundred twenty-four male and 100 female workers provided blood samples for polymerase chain reaction analysis and completed the questionnaire. We performed a stepwise logistic regression analysis to discriminate between the typical homozygote (ALDH2*1/*1) and the atypical heterozygote (ALDH2*1/*2) in male subjects. Because of the limitation in the sample size for ALDH2*2/*2, this genotype was not included in the analysis. Results revealed that only three symptoms (facial flushing, flushing elsewhere, and palpitation) were enough to correctly predict the ALDH2 genotypes in approximately 89% of all subjects. The present questionnaire method (ALcohol Sensitivity screening Test; ALST) takes a little time and effort for the genotype determination, and may be especially useful in epidemiological studies with a large sample size or with subjects from whom DNA samples are not available.

Adult↗
PubMed2005

Psychosocial, cultural and genetic influences on alcohol use in Asian American youth.

OBJECTIVE: Environmental and cultural factors, as well as a genetic variant of the aldehyde dehydrogenase gene (the ALDH2*2 allele) have been identified as correlates of alcohol use among Asian Americans. However, concurrent examination of these variables has been rare. The present study assessed parental alcohol use, acculturation and ALDH2 gene status in relation to lifetime, current and heavy episodic drinking among Chinese and Korean American undergraduates. METHOD: Participants (N = 428, 51% women; 52% Chinese American, age 18-19 years) were first-year college students in a longitudinal study of substance use initiation and progression. Data were collected via structured interview and self-report, and participants provided a blood sample for genotyping at the ALDH2 locus. RESULTS: Gender, parental alcohol use and acculturation significantly predicted drinking behavior. However, none of the hypothesized moderating relationships were significant. In contrast with previous studies, ALDH2 gene status was not associated with alcohol use. CONCLUSIONS: Results indicate that although the variables examined influence alcohol use, moderating effects were not observed in the present sample of Asian American college students. Findings further suggest that the established association of ALDH2 status and drinking behavior in Asians may not be evident in late adolescence. It is possible that ALDH2 status is associated with alcohol consumption only following initiation and increased drinking experience.

Acculturation↗
PubMed1997

Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde dehydrogenase.

BACKGROUND: About half of certain Asians have a deficiency of the low-Km aldehyde dehydrogenase (ALDH2) isoenzyme. This deficiency results from inheritance of a mutant ALDH2*2 allele. OBJECTIVE: To determine whether Asian Americans with ALDH2*2 alleles differ from Asian Americans without this mutation in terms of blood levels of alcohol and acetaldehyde after ingestion of a moderate amount of alcohol. DESIGN: Double-blind, crossover study. SETTING: Private research institute. PARTICIPANTS: 35 healthy Asian-American men. Three men who became ill after alcohol ingestion and one who had outlying data were excluded. INTERVENTION: Alcoholic beverage, containing 0.56 g of alcohol per kg of body weight, or placebo beverage, containing 3 mL of alcohol, given orally on separate occasions. MEASUREMENTS: Blood levels of alcohol and acetaldehyde measured before and several times after ingestion of the alcoholic or placebo beverage. RESULTS: Participants with ALDH2*2 alleles had significantly higher blood acetaldehyde levels after ingesting alcoholic and placebo beverages than did participants with ALDH2*1 alleles, despite similar blood alcohol concentrations. CONCLUSIONS: Blood acetaldehyde levels rather than blood alcohol concentration may mediate enhanced alcohol sensitivity among Asians with ALDH2*2 alleles.

Acetaldehyde↗
PubMed1999

No association between DRD2 locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population.

BACKGROUND: Recent studies on the genetics of alcoholism have examined the association between alcoholism and the dopamine D2 receptor locus (DRD2); our study of Chinese Han gave negative results (Lu et al., 1996). The different genotypes at the genes encoding the enzymes involved in alcohol metabolism, class one alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2), have previously been shown to confer different predispositions to the development of alcoholism in Chinese Han males (Thomasson et al., 1991; Chen WJ et al., 1996; Chen CC et al., unpublished data). Therefore, association studies of alcoholism in Chinese Han might be more sensitive if controlled for the genotypes of ADH2,ADH3, and ALDH2, when other loci, such as DRD2, are examined. This study employs such controls to evaluate the evidence for an association between alcoholism and TaqI-A and TaqI-B genotypes and haplotypes at DRD2 in the Chinese Han population. METHODS: We studied 213 Chinese Han subjects (128 alcoholics and 85 nonalcoholics) with alcohol dependence defined according to DSM-III-R criteria. RESULTS: Significant linkage disequilibrium was observed between the TaqI-A and TaqI-B sites at the DRD2 locus, as previously seen in smaller samples, but no significant association was observed between these genetic variants at the DRD2 locus and alcoholism in Chinese Han. Several different stratifications by ADH and ALDH2 genotypes were examined; no genotypes or haplotypes at DRD2 differ between alcoholics and nonalcoholics except for a small number of nominally significant p-values which do not constitute significant results given the many tests done, some of which are not independent of one another due to linkage disequilibrium. These tests included considering the high risk (ADH2*1/*1; *1/*2; ADH3*1/*2; *2/*2; and ALDH2*1/*1) and the low risk (ADH2*2/*2; ADH3*1/*1; and ALDH2*1/*2; *2/*2) groups of alcoholics, as well as nonalcoholic controls. CONCLUSIONS: After stratification by the relevant genotypes of ADH2, ADH3, and ALDH2 no significant association exists between the genetic variants at the DRD2 locus and alcoholism in the Chinese Han population.

Alcohol Dehydrogenase↗
PubMed2001

Association of the ADH2 genotypes with skin responses after ethanol exposure in Japanese male university students.

BACKGROUND: A contribution of the alcohol dehydrogenase-2 (ADH2) polymorphism to alcohol sensitivity and alcohol drinking behavior is still controversial. In this study, we examined the effects of the ADH2 genotypes on skin reactions to ethanol and habitual alcohol intake among Japanese male university students, controlling for the effects of the low Km aldehyde dehydrogenase (ALDH2) genotype, as an extension of our previous study. METHODS: The study subjects were 357 Japanese male students [average age (mean +/- SD) was 23.7 +/- 3.0 years] in a medical university. The subjects completed a questionnaire regarding self-reported alcohol-associated symptoms and alcohol-drinking behavior. The ADH2 and ALDH2 genotypes were determined through digestion of polymerase chain reaction products by restriction enzymes. All subjects participated in the ethanol patch test. We observed skin responses at 0, 5, 15, and 20 min after removal of the tape. RESULTS: Among the ALDH2*1/*1 genotypes, only some subjects with ADH2*1/*2 or ADH2*2/*2 exhibited a positive response, which increased with increasing time after the removal. However, none of comparisons between the different ADH2 genotypes reached statistical significance. Among the ALDH2*1/*2 genotypes, those with ADH2*1/*2 or ADH2*2/*2 showed a significant increase in response with increasing time after the removal and revealed a significantly higher positivity rate at 15 min than those with ADH2*1/*1. In those with the ALDH2*1/*2 genotype, the positive rate of facial flushing with one glass of beer was higher in those with ADH2*1/*2 and ADH2*2/*2 than those with ADH2*1/*1, although this was not significant. However, the ADH2 genotype did not seem to influence drinking frequency or amounts of alcohol intake in each ALDH2 genotype. CONCLUSIONS: This study finds further evidence for a contribution of the ADH2 polymorphism to skin reactions after either local or systemic ethanol exposure in Asian people. However, the effects of the ADH2 polymorphism may be mild because this polymorphism does not seem to influence alcohol drinking behavior in these study subjects.

Adult↗
PubMed1992

[ALDH phenotype in eating disorders with and without alcoholism].

Individuals who have inactive low Km aldehyde dehydrogenase (ALDH2) are much less likely to develop alcoholism than those who have active ALDH2. On the other hand, frequent alcoholism has been reported in eating disorder patients. Whether inactive ALDH2 works as an inhibitory factor for alcoholism in these patients is not known. We compared the ALDH2 phenotype in eating disorder patients with and without alcoholism. Among the 25 subjects (4 with anorexia nervosa, 6 with anorexia nervosa and bulimia nervosa, 13 with bulimia nervosa and 2 with eating disorder not otherwise specified according to the DSM-III-R), 13 were alcoholics and 12 were non-alcoholics. Isoelectric focusing of hair roots samples demonstrated that 8% of the alcoholic subjects had the inactive ALDH2, while 58% of the non-alcoholic subjects had this variant form of the isozyme (p < 0.01). The results suggest inactive ALDH2 has a similar inhibitory effect for alcoholism as in eating disorder patients as has been reported in normal populations.

Adult↗
PubMed2005

[Polymorphism of alcohol metabolizing-related enzyme genes and its correlation with drinking-behaviors in 201 cases of Chinese Han healthy population].

OBJECTIVE: To study the distribution of genotypes about alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) and its relationship with drinking-behaviors in Chinese Han healthy population as to providing a theoretic direction for filtering out high-risk and sensitive individuals and taking preventive measures to decrease the alcohol-related diseases. METHODS: Using questionnaires to select subjects (201 persons, including men 104, women 97) for collecting blood samples and data about drinking-behaviors. Techniques of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect the genotypes of ADH2 and ALDH2. RESULTS: Heterozygous ADH2 and homozygous ALDH2 were the two dominant ones (respectively 53.23%, 68.16%). There were no statistical differences among the distributions of nine combinations of ADH2 genotypes and ALDH2 ones. The difference of distribution of homozygous ALDH2 between males having high and middle drinking-frequencies seemed to be statistically meaningful. CONCLUSION: The proportion of individuals carrying about "susceptible genotypes of alcohol-related diseases" in Chinese Han healthy population should be more than one half (68.16%), which calls on reinforcing the surveillance and preventing the alcohol-related diseases. Correlation between genotypes of ADH2 and ALDH2 and alcohol-related diseases should be more important.

Adolescent↗
PubMed1988

Localization of cytoplasmic and mitochondrial aldehyde dehydrogenase isozymes in human liver.

Aldehyde dehydrogenase isozymes (ALDH1 or E1 and ALDH2 or E2 according to the classification by Greenfield NJ, Pietruszko R, Biochim Biophys Acta 483:35, 1977) were purified from the human liver to homogeneity by the use of ion exchange chromatography on CM-Sephadex, DEAE-Sephadex, and QAE-Sephadex and affinity chromatography on 5'-AMP Sepharose 4B, and preparative isoelectric focusing agarose electrophoresis. These were injected in rabbits to elicit antibodies against ALDH1 and ALDH2, respectively and their specificities were tested by double immunodiffusion. By gel filtration, the antibodies were separated into F'ab fragments, conjugated with horseradish peroxidase, and served to detect ALDH1 and ALDH2 proteins in normal liver tissue. Immunoelectron microscopy by the preembedding method revealed that the electron-dense materials reacted with anti-ALDH1 antibody were located in the cytoplasm of hepatocytes, mainly around the nuclear membrane, mitochondria, and endoplasmic reticulum; in the mitochondria, however, no staining was demonstrated. In contrast, the reaction with anti-ALDH2 antibody was observed only in the mitochondria. Immunostaining, performed by the enzyme-labeled antibody method demonstrated that in the hepatic lobule, there were no differences of the intensity of ALDH1 antigenicity and that of ALDH2 antigenicity between periportal (zone 1) and pericentral (zone 3) hepatocytes. These results suggest that in the human liver ALDH1 and ALDH2 are distributed equally in the periportal and centrilobular regions.

Aldehyde Dehydrogenase↗
PubMed1994

[Association among genotypes of aldehyde dehydrogenase 2 and alcohol consumption].

A large population survey was made for the determination of aldehyde dehydrogenase 2 (ALDH2) genotypes among 630 unrelated Japanese adults by PCR using allele specific primers. The frequencies of three genotypes were 60% ALDH2*1/ALDH2*1 (NN) type, 35% ALDH2*1/ALDH2*2 (ND) type and 5% ALDH2*2/ALDH2*2 (dd) type. Average amounts of alcohol consumption per month for three genotypes were 965.8 g/month for NN type, 629.5 g/month for ND type and 179 g/month for DD type. The differences in average alcohol consumption were significant (p < 0.01) among the three genetic different groups. When male and female date were analyzed separately for these three groups, significant differences among three groups were found in both genders. These results indicated that ALDH2 mutant is an important genetic factor for limiting the alcohol consumption. The frequencies of ALDH2 genotypes were not significantly different between male and female population groups, however, their average alcohol consumption were significantly different between the two groups. Therefore, various social factors and life styles, in addition to genetic factors, might concern in the difference of alcohol consumption.

Adult↗
PubMed1996

Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males.

Although drinking alcohol is an established esophageal cancer risk factor, the mechanisms by which alcohol induces this high-mortality rate cancer are not clear. To help elucidate this problem and develop an implementable preventive strategy, this genetic epidemiological study focused on aldehyde dehydrogenase 2 (ALDH2), the key enzyme for elimination of acetaldehyde generated by alcohol consumption. This enzyme is polymorphic; its mutant allele, ALDH2*2, which leads to the enzyme inactivity, is prevalent in Orientals. This Japanese case-control study of ALDH2-related risk for esophageal squamous cell carcinoma included alcoholics (40 cases and 55 controls) and nonalcoholic drinkers (29 cases and 28 controls). The analysis of the results of genotyping these subjects showed that the increased risk for esophageal cancer in those with one ALDH2*2 allele was substantially higher in both alcoholics (odds ratio = 7.6; 95% confidence interval = 2.8-20.7) and nonalcoholic drinkers (odds ratio = 12.1; 95% confidence interval = 3.4-42.8). The results strongly suggest that because persons who have this mutant ALDH2*2 allele have a high concentration of blood acetaldehyde after drinking alcohol, acetaldehyde (a recognized animal carcinogen) plays a pivotal role in the pathogenesis of alcohol-related esophageal cancer in humans. These results suggest that to help lower their risk for esophageal cancer, persons with the ALDH2*2 allele should be encouraged to reduce their consumption of alcoholic beverages.

Acetaldehyde↗
PubMed1997

Genetic polymorphism of cytochrome P-4502E1 and mitochondrial aldehyde dehydrogenase in a Korean population.

Mitochondrial aldehyde dehydrogenase (ALDH2) is mainly responsible for the oxidation of acetaldehyde generated during alcohol oxidation in vivo. Cytochrome P-4502E1 (CYP2E1), a liver microsomal enzyme, also metabolizes acetaldehyde and ethanol. Genetic polymorphism of ALDH2 and CYP2E1 was investigated among 481 Korean adults. A new restriction fragment-length polymorphism method was developed to determine the genotype of the ALDH2 alleles. This method proved to be simpler and faster than the hybridization method using allele-specific oligonucleotide probes and polymerase chain reaction-directed mutagenesis. The allele frequencies of ALDH2(1) and ALDH2(2) were 0.840 and 0.160, respectively. This allele frequency of ALDH2(2) is less than in Japanese people. Genetic polymorphism of CYP2E1 was investigated using polymerase chain reaction and restriction fragment-length polymorphism. The estimated allele frequencies for c1 and c2 were 0.808 and 0.192.

Adult↗