Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ALDH2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1998

Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers.

Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. VCM may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferases (GSTs). Thus workers with inherited variant metabolic enzyme activities may have an altered risk of genotoxicity. This study was designed to investigate which risk factors might affect sister chromatid exchange (SCE) frequency in polyvinyl chloride (PVC) workers. Study subjects were 44 male workers from three PVC factories. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. SCE frequency in peripheral lymphocytes was determined using a standardized method, and CYP2E1, GSTM1, GSTT1 and ALDH2 genotypes were identified by the polymerase chain reaction (PCR). Analysis revealed that smoking status and exposure to VCM were significantly associated with increased SCE frequency. The presence of ALDH2 1-2/2-2 genotypes was also significantly associated with an elevation of SCE frequency (9. 5 vs. 8.1, p<0.01). However, CYP2E1, GSTM1 or GSTT1 genotypes were not significantly associated with SCE frequency. When various genotypes were considered together, combination of CYP2E1 c1c2/c2c2 with ALDH2 1-2/2-2 showed an additive effect on SCE frequency. Similar results were also found for the combination of smoking with CYP2E1, or smoking with ALDH2. These results suggest that VCM workers with ALDH2 1-2/2-2 genotypes, who also smoke, may have increased risk of DNA damage.

Adult↗
PubMed1996

Cancer screening of upper aerodigestive tract in Japanese alcoholics with reference to drinking and smoking habits and aldehyde dehydrogenase-2 genotype.

In this study, 1,000 Japanese male alcoholics were consecutively screened by upper gastrointestinal endoscopy with esophageal iodine staining. Associations among cancer-detection rates, drinking and smoking habits, and aldehyde dehydrogenase-2 (ALDH2) genotypes were evaluated. A total of 53 patients (5.3%) had histologically confirmed cancer. Esophageal cancer was diagnosed in 36, gastric cancer in 17, and oropharyngolaryngeal cancer in 9 patients: 8 of the esophageal-cancer patients were multiple-cancer patients, with additional cancer(s) in the stomach and/or oropharyngolaryngeal region. Multiple logistic regression revealed that use of stronger alcoholic beverages (whisky or shochu) in contrast with lighter beverages (sake or beer) and smoking of 50 pack-years or more increased the risks for esophageal (odds ratio 3.2 and 2.8 respectively), oropharyngolaryngeal (4.8 and 5.1 respectively) and multiple cancer (10.5 and 11.8 respectively). The inactive form of ALDH2, encoded by the gene ALDH2*1/2*2 prevalent in Orientals, exposes them to higher blood levels of acetaldehyde, a recognized animal carcinogen, after drinking. This inactive ALDH2 was detected in 19/36 (52.8%) patients with esophageal cancer, in 5/9 (55.6%) patients with oropharyngolaryngeal cancer, and in 7/8 (87.5%) patients with multiple cancer. All of these gene frequencies far exceeded that in a large alcoholic cohort (80/655, 12.2%). The triple combination of the risk factors of the inactive ALDH2, stronger alcoholic beverages and heavy smoking was more commonly associated with multiple-cancer patients than with patients with esophageal cancer alone (62.5% vs. 7.1%). These results show that the 3 risk factors are important for the development of upper-aerodigestive-tract cancer in Japanese alcoholics. For these high-risk drinkers, regimented screening appears to be indicated.

Adult↗
PubMed2006

Dietary selenium intake, aldehyde dehydrogenase-2 and X-ray repair cross-complementing 1 genetic polymorphisms, and the risk of esophageal squamous cell carcinoma.

BACKGROUND: To the authors' knowledge, few studies have been conducted to date regarding dietary selenium and the potential gene-nutrient interactions with single-nucleotide polymorphisms (SNPs) in different pathways on the risk of esophageal cancer. METHODS: The authors investigated the role of dietary selenium intake and its interplay with SNPs of the ALDH2 (glutamic acid [Glu] 487 lysine [Lys]) and the X-ray repair cross-complementing 1 (XRCC1) (arginine [Arg] 399 glutamine [Gln]) genes on the risk of esophageal squamous cell carcinoma (ESCC) in a population-based, case-control study in China. In total, 218 patients with ESCC and 415 healthy population control participants were interviewed. Dietary selenium intake was estimated from a food frequency questionnaire with 97 food items. ALDH2 and XRCC1 polymorphisms were detected with a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The adjusted odds ratio (OR) for the highest quintile of dietary selenium intake, compared with the lowest quintile of intake, was 0.48 (95% confidence interval [95% CI], 0.25-0.89), with a strong dose-response relation (P for trend, <.01). The ALDH2 Lys and XRCC1 Gln variant alleles were associated with an increased risk of ESCC with adjusted ORs of 1.91 (95% CI, 0.96-3.80) and 1.67 (95% CI, 1.08-2.59), respectively. An elevation of the risk for ESCC was pronounced most among carriers of ALDH2 Lys/Lys and XRCC1 399Gln/Gln or Gln/Arg who consumed a low level of dietary selenium (adjusted OR, 4.16; 95% CI, 1.14-15.12). CONCLUSIONS: To the authors' knowledge, this is the first in-depth study to suggest that genetic susceptibility may modify the association between selenium intake and the risk of ESCC. The findings indicated that individuals with low dietary selenium intake and ALDH2 Lys/Lys and XRCC1 399Gln/Gln or Gln/Arg genotypes were associated with an increased ESCC risk, especially in the presence of exposure to tobacco and alcohol carcinogens.

Aged↗
PubMed1993

The mitochondrial aldehyde dehydrogenase gene resides in an HTF island but is expressed in a tissue-specific manner.

The tissue distribution of mitochondrial aldehyde dehydrogenase (ALDH2) in rats was analyzed by activity assays, and by Western and Northern blotting. ALDH2 was expressed at highest levels in liver. The mRNA levels were intermediate in the kidney and lung, while lower levels were found in spleen and heart. The transcript was undetectable in other tissues tested. The human ALDH2 5' flanking region (-200 to +60) contains similar numbers of CpG and GpC dinucleotides and the rat ALDH2 gene was undermethylated in liver, kidney, and spleen. This suggests that the ALDH2 promoter resides in a Hpa II tiny fragment (HTF) island, unlike most genes expressed in a tissue-specific manner.

Aldehyde Dehydrogenase↗
PubMed2002

Lifestyle habits and genetic susceptibility and the risk of esophageal cancer in the Thai population.

The association of lifestyle habits and polymorphism of ADH2 and ALDH2 genes with the risk of esophageal cancer in Thai population was investigated in a hospital-based case-control study: 202 cases and 261 controls. The results of multivariate logistic analysis showed that alcohol consumption >60g/day, smoking >10 cigarettes/day and chewing betel >or=10 quids/day significantly increased risk (odds ratio (OR) 5.84, 95% confidence interval (CI) 3.15-10.83; 4.65, 95% CI 1.99-10.84; and 4.68, 95% CI 2.05-10.72, respectively). ADH2*1/*1 also increased the risk significantly (OR 1.56, 95% CI 1.01-2.39) while ALDH2 did not (OR of ALDH2*1/*2 1.57, 95% CI 0.89-2.76). However, the combined at risk genotypes, ADH2*1/*1 and ALDH2*1/*2 increased risk to four-fold. In addition, significant gene-environment interaction was found. Heavy drinkers >60g/d harboring ADH2*1/*1 or ALDH2*1/*2 had about an 11-fold increased risk.

Adult↗
PubMed2002

Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency.

An aldehyde-dehydrogenase (ALDH2) deficiency is a biological curb on excess alcohol-drinking. This enzyme deficiency is very common amongst Oriental people while it is relatively rare for most other populations. We observe that there is good geographical correlation between the prevalence of the mutant ALDH2*2 alleles and hepatitis B virus (HBV) infections. Populations that demonstrate a high ALDH2*2 prevalence are all located in HBV-endemic areas. Further, studies have shown that HBV and alcohol drinking exhibit a synergistic effect upon liver cirrhosis and cancer. A shorter life span for those with HBV infection and heavy alcohol consumption may result in a selection of the ALDH2*2 gene. We postulate that there may be patterns of evolutionary adaptation for ALDH2 deficiency in certain HBV-endemic areas and that these adaptations can produce differences in human alcohol-drinking capability.

Alcohol Drinking↗
PubMed2003

Organ-specific expressions and chromosomal locations of two mitochondrial aldehyde dehydrogenase genes from rice (Oryza sativa L.), ALDH2a and ALDH2b.

Recent studies have suggested that mitochondrial aldehyde dehydrogenase (aldehyde:NAD(P)(+) oxidoreductase, EC 1.2.1.3) (ALDH2) plays essential roles in pollen development in plants. Rice (Oryza sativa L.) ALDH2 is encoded by at least two ALDH2 genes, one of which (ALDH2a) was previously identified. In this study, to understand the roles of ALDH2 in rice, we isolated and characterized a cDNA clone encoding another rice ALDH2 (ALDH2b). An in vitro ALDH assay indicated that ALDH2b possesses an NAD(+)-linked activity for oxidation of acetaldehyde, glycolaldehyde and propionaldehyde. Northern blot and immunoblot analyses revealed that ALDH2b was constitutively present in all the organs examined, whereas ALDH2a was expressed in leaves of dark-grown seedlings and panicles. By RFLP linkage mapping, the ALDH2a and ALDH2b genes were mapped to the long arm of chromosome 2 and the short arm of chromosome 6, respectively. We suggest that the rice ALDH2a and ALDH2b genes are orthologues of maize mitochondrial ALDH genes, rf2b and rf2a, respectively.

Aldehyde Dehydrogenase↗
PubMed2001

A genetic association with the development of alcohol and other substance use behavior in Asian Americans.

Studies of Asian adults have found that alcohol use and alcohol dependence are related to variation in the aldehyde dehydrogenase (ALDH2) gene. To investigate the association of ALDH2 with the development of drug involvement, the authors analyzed retrospective information about the onset and regular use of alcohol and other substances as reported by 180 Asian American college students. Possession of an ALDH2*2 allele was not related to initiation of alcohol use or having ever been intoxicated, but individuals with ALDH2*2 alleles were less likely to be regular drinkers, were less likely to have engaged in a binge-drinking episode, reported a lower number of maximum drinks consumed in a 24-hr period, and were less likely to have used tobacco regularly than those without this genetic variant. These findings suggest that ALDH2 is associated with the development of not only alcohol-related behavior but other substance use behavior as well.

Adult↗
PubMed1999

Aldehyde dehydrogenase genotypes and male alcohol use disorders: a case-control study in Khon Kaen, north-east Thailand.

A genetic epidemiological case-control study on aldehyde dehydrogenase 2 (ALDH2) genotype and male probable alcohol use disorders (AUD) was performed in Khon Kaen province, northeast Thailand. One hundred and twenty-four of cases (probable AUD) were obtained from male villagers aged 18-65 years using the modified Michigan Alcoholism Screening Test-Thai version. The same number of controls were selected, being matched with the cases in terms of age (+/-4 years) within the same village. Marital status, education history and past or present histories of physical illnesses were essentially the same for the cases and the controls. All of the cases and 85.5% of the controls were current drinkers, and the cases tended to drink significantly more often than the controls. Genomic DNA was extracted from fingernails and ALDH2 genotypes were determined by polymerase chain reaction technique and digested by Ksp 632I. The ALDH2 genotypes of the cases and the controls were not significantly different: 90.3% versus 91.1% normal homozygote; 8.1% versus 8.9% heterozygote; and 1.6% versus 0.0% mutant homozygote, respectively. Among the normal homozygote, the daily amount of alcohol intakes of the cases were significantly larger than that of the controls (56.2+/-40.6g vs. 8.1+/-14.1 g), the same was found among the ALDH2 deficient (55.9+/-43.4 vs. 2.2+/-5.8 g). Multivariate analysis based on the conditional logistic regression model showed no significant association of AUD with ALDH2 genotype, marital status, education history, or past history of injury, however, occupation and daily amount of alcohol intake were found to be significantly associated with AUD (OR = 10.72, 95% CI = 1.15-99.99, P = 0.037, and OR = 1.12, 95% CI = 1.06-1.18, P = 0.000, respectively). Non-farmers showed 10.7 times larger risk of developing AUD compared to farmers, and the subjects had three times more chance of developing AUD for each increase of 10 g of the daily amount of alcohol intake.

Adult↗
PubMedDate not supplied

Investigation of alcohol metabolizing enzyme genes in Chinese alcoholics with avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver.

AIMS AND METHODS: Alcoholism may cause a range of diseases including avascular necrosis of the hip joint (AVN), cirrhosis of the liver, pancreatitis and oesophageal carcinoma. Chinese alcoholic patients diagnosed with AVN have a higher incidence of cirrhosis than of acute pancreatitis or oesophageal cancer. Thus, the aim of this study was to investigate genetic differences in polymorphisms of the alcohol-metabolizing enzymes ADH2, ADH3, ALDH2 and P4502E1 for subgroups of Chinese alcoholic patients, defined by diagnoses of AVN (n = 51), acute pancreatitis (n = 92) and liver cirrhosis (n = 159), and for 280 non-alcoholic patients. RESULTS: Analysis revealed that ADH2*1 allele frequency was significantly lower for the alcoholic AVN than for the cirrhosis subgroup. However, no significant difference was found between the alcoholic AVN and pancreatitis subgroups. Furthermore, ALDH2*2 prevalence was not found to differ significantly between the alcoholic subgroups. When compared with our previously published data for alcoholic patients with oesophageal carcinoma, ADH2*1 carriage was significantly less frequent for the alcoholic AVN patients in the current study. Further, ALDH2*2 carriage was significantly less frequent for the alcoholic AVN subgroup than for the oesophageal carcinoma patients. CONCLUSIONS: The allele frequencies for ADH2*1 and ALDH2*2 are different when comparing subpopulations of alcoholics defined by presence of specific alcohol-induced diseases, suggesting that genetic variation in alcohol-metabolizing enzyme genes accounts for, at least in part, the specific types of organ damage observed. We also found the combination of AVN and cirrhosis to be more prevalent than that of AVN and acute pancreatitis. In contrast, the ADH2 and ALDH2 allele frequencies for the AVN subgroup were more similar to those of the acute-pancreatitis than to the cirrhosis subgroup. These data indicate the possibility that other genetic variations may also influence the type of organ-specific complications in Chinese alcoholics.

Adult↗
PubMed2002

Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer.

Patients with squamous-cell carcinoma in the head and neck (HNSCC) often develop second primary esophageal squamous-cell carcinomas (ESCC). In addition, widespread epithelial oncogenic alterations are also frequently observed in the esophagus and can be made visible as multiple Lugol-voiding lesions (multiple LVL) by Lugol chromoendoscopy. Multiple occurrences of neoplastic change in the upper aerodigestive tract have been explained by the concept of 'field cancerization', usually associated with repeated exposure to carcinogens such as alcohol and cigarette smoke. However, the etiology of second ESCC in HNSCC patients remains unclear and acetaldehyde, the first metabolite of ethanol, has been implicated as the ultimate carcinogen in alcohol-related carcinogenesis. We first investigated the relation between second ESCC and multiple LVL in 78 HNSCC patients. Multiple LVL and second ESCC were observed in 29 (37%) and 21 (27%) patients, respectively. All of the second ESCC were accompanied by multiple LVL. This may indicate that episodes of multiple LVL are precursors for second ESCC. We then examined the association of multiple LVL with the patients' characteristics, including genetic polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2). We also investigated acetaldehyde concentrations in the breath of 52 of the 78 patients. All the patients with multiple LVL were both drinkers and smokers. Multivariable logistic analysis showed that the inactive ALDH2 allele (ALDH2-2) was the strongest contributing factor for the development of multiple LVL (odds ratio 17.6; 95% confidence intervals 4.7-65.3). After alcohol ingestion, acetaldehyde in the breath was elevated to a significantly higher level in all patients with the ALDH2-2 allele than in those without it. The high levels of breath acetaldehyde were significantly modified by the slow-metabolizing ADH3-2 allele. These results reveal strong evidence for a gene-environmental interaction between the ALDH2-2 allele and alcohol consumption, for the risk of developing multiple LVL, resulting in the development of second ESCC in patients with HNSCC. Ultimately, increased local acetaldehyde exposure thus appears to be a critical determinant of the phenomenon of 'field cancerization'.

Alcohol Drinking↗
PubMed2003

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers.

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. 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. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.

Alcohol Dehydrogenase↗
PubMed1997

Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility.

Many human cancers are caused by synthetic or natural chemical compounds in the environment. Esophageal squamous cell carcinoma has been reported to be epidemiologically associated with tobacco and alcohol consumption. We studied the association between genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and esophageal squamous cell carcinoma susceptibility. We examined genetic polymorphisms of the CYPIA1, GSTM1, CYPIIE1, ADH2, and ALDH2 genes in 94 Japanese patients with esophageal squamous cell carcinoma and 70 unrelated healthy Japanese persons. There were no significant differences between healthy controls and patients with esophageal cancer in the polymorphisms of the CYPIA1, GSTM1, and CYPIIE1 genes. On the other hand, there were significant differences in the ADH2 and ALDH2 polymorphisms between healthy controls and esophageal cancer patients. The ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) genotypes were independently and significantly higher in esophageal cancer patients than in healthy controls. Furthermore, persons with the combined genotypes ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) were at extraordinarily high risk for esophageal squamous cell carcinoma, with an odds ratio of 17.9 (p < 0.001). Thus polymorphisms of alcohol-metabolizing enzymes, that is, ADH2 and ALDH2, may be useful for screening patients at high risk for esophageal cancer, which might facilitate clarification of esophageal tumorigenesis and prevention of esophageal cancer.

Alcohol Dehydrogenase↗
PubMed2001

Association between smoking, acetaldehyde dehydrogenase-2 1-1 status, and alcohol drinking among Taiwanese polyvinyl chloride workers.

To study the factors affecting alcohol consumption among Taiwanese workers, we conducted an investigation of the association between alcohol drinking and smoking, aldehyde dehydrogenase-2 (ALDH2) status, alcohol dehydrogenase-2 (ADH2) status, any history of abnormal liver function, and hepatitis B and C viral infection. The subjects included 207 male workers who had been followed-up with respect to liver function periodically since 1992. Information relating to current alcohol consumption and smoking habits was obtained by an interviewer-administered questionnaire in 1996, and any history of liver function and hepatitis B and C virus infection was obtained from previous medical surveillance. Genotypes of ALDH2 and ADH2 were determined by polymerase chain reaction/restriction fragment polymorphism assay. Results have revealed that smoking and ALDH2 1-1 status were associated with current alcohol consumption (respectively: odds ratio, 23.3; P < 0.01 and odds ratio, 14.5; P < 0.05). Neither a history of abnormal liver function nor a history of hepatitis B and/or C infection was associated with current alcohol consumption. It seems that only those with ALDH2 1-1 who are smokers consume alcohol. We conclude that smoking and inherited ALDH2 1-1 are the most important determinants of alcohol consumption. In addition to the medical advice of physicians in their yearly health check-ups, worksite health-promotion programs based on both alcohol consumption habits and smoking cessation should be instituted forthwith, particularly for those who demonstrate the potential for developing liver damage.

Adult↗
PubMed2005

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese.

The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.

Adult↗
PubMed1999

Relationship between serum levels of anti-low-density lipoprotein-acetaldehyde-adduct antibody and aldehyde dehydrogenase 2 heterozygotes in patients with alcoholic liver injury.

We prepared low-density lipoprotein (LDL)-acetaldehyde-adduct (hereafter abbreviated as LDL-adduct) and anti-LDL-adduct antibody by using Watanabe hyperlipidemic rabbits, and determined values of serum anti-LDL-adduct antibody levels by the ELISA method in healthy adults and patients with alcoholic liver injury. In the nondrinking group in healthy adults, values of anti-LDL-adduct antibody levels were 25 +/- 13 microg/ml, and there was no significant difference between moderate drinkers without diseases and the nondrinking group in healthy adults. Values of anti-LDL-adduct antibody in alcoholic disease groups, 17 +/- 9 microg/ml for the patients with the fatty liver group, 21 +/- 14 microg/ml for the hepatic fibrosis group, 70 +/- 21 microg/ml for the alcoholic hepatitis group, 41 +/- 50 microg/ml for the alcoholic cirrhosis group, and 19 +/- 18 microg/ml for the alcoholic pancreatitis group. Examinations of aldehyde dehydrogenase 2 (ALDH2) genetic variations by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method in the healthy group and the liver injury group revealed a tendency for patients with ALDH2(1)/2(2) in the liver injury group to have relatively mild liver lesions. When comparing anti-LDL-adduct antibody levels between ALDH2 genetic variations, those for the patients with ALDH2(1)/2(2) (36 +/- 40 microg/ml) were significantly higher than those for patients with ALDH2(1)/2(2) (11 +/- 5 microg/ml). Results of the present study suggest that genetic variation may influence the progression of liver injury.

Acetaldehyde↗
PubMed2002

Effects of aldehyde dehydrogenase-2 genetic polymorphisms on metabolism of structurally different aldehydes in human liver.

Genotype analysis of the aldehyde dehydrogenase (ALDH)-2 gene was performed using an improved simplified method, and effects of the genotype on the metabolism of a variety of aldehydes in different fractions of human liver cells were investigated. The effects of sex, aging, smoking, drinking alcohol, liver function, and various drugs on ALDH activity were also analyzed. Of the 39 subjects, eight were heterozygotes of the wild (ALDH2*1) and mutant (ALDH2*2) alleles, and the others were homozygotes of the wild allele. ALDH activity toward acetaldehyde in liver mitochondria from subjects with a mutant allele was less than 10% of that with two alleles of wild-type, and the activities toward formaldehyde, propionaldehyde, n-butyraldehyde, capronaldehyde, and heptaldehyde were also significantly lower in the ALDH2*1/*2 rather than ALDH2*1/*1 group. However, the metabolism of octylaldehyde, decylaldehyde, retinaldehyde, benzaldehyde, 3-hydroxybenzaldehyde, and 2,5-dihydroxybenzaldehyde was similar in the two genotypes. Changes in activity in the cytosolic fraction were similar to those in mitochondria. There was no significant difference in ALDH activity in microsomes between the two groups. Total activities of ALDH toward acetaldehyde and other short-chain aliphatic aldehydes in supernatant fractions of homogenized liver were affected in a manner similar to that in mitochondria. Our results suggest that the single nucleotide polymorphisms of the ALDH2 gene only alter the metabolism of aldehydes with a short aliphatic chain. Furthermore, sex, drinking alcohol, and smoking had little effect on ALDH activity, although the activity in elderly individuals tended to be lower albeit statistically insignificant.

Aging↗
PubMed2000

Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.

BACKGROUND: Multiple occurrences of oesophageal dysplasia are frequently observed in head and neck cancer patients, and closely associated with alcohol consumption. Acetaldehyde, the first metabolite of ethanol, is thought to play an important role in the carcinogenesis of the upper aerodigestive tract. AIM: To investigate if genetic polymorphism in alcohol metabolising enzymes (ADH3, alcohol dehydrogenase 3; ALDH2, aldehyde dehydrogenase 2) is associated with oesophageal multiple dysplasia in head and neck cancer patients. METHODS: Thirty one consecutive patients with head and neck cancer were included in the study. Multiple oesophageal dysplasia was detected endoscopically as multiple Lugol voiding lesions (multiple LVL) using the Lugol dye staining method. The ADH3 and ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Among the 31 patients with head and neck cancer, 17 had multiple LVL. Multiple LVL were closely associated with a second primary oesophageal carcinoma in head and neck cancer patients (odds ratio 60.7, 95% CI 5.6-659). Furthermore, the mutant ALDH2 allele was significantly more prevalent in patients with multiple LVL (65% v 29%; p<0.05) whereas no difference was observed in ADH3 polymorphism. CONCLUSIONS: The mutant ALDH2 allele appears to be a risk indicator for multiple LVL in head and neck cancer patients. Accumulation of acetaldehyde due to low ALDH2 activity may play a critical role in cancerous changes throughout the mucosa in the upper aerodigestive tract.

Aged↗