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PubMed1994

[Individual differences in the sensitivity to the effect of alcohol upon pain].

In this study, the relationship between pain threshold and blood ethanol level, and also the effect of alcohol sensitivity upon the threshold was investigated. Thirty-one healthy subjects, aged 20 to 62 years, were studied. The genotypes at the aldehyde dehydrogenase 2 (ALDH) locus were determined in each subject to evaluate the alcohol sensitivity. The subjects were divided into three groups based on the ALDH2 genotypes, i.e., the ALDH2*1/*1 (homozygous active ALDH), the ALDH2*1/*2 (heterozygous inactive ALDH) and the ALDH2*2/*2 (homozygous inactive ALDH). The subjects were given orally 0.4 g.kg-1 and/or 0.8 g.kg-1 of ethanol. Venous blood samples were collected at 30, 60, 120, 180, and 240 min after ethanol intake and blood ethanol and acetaldehyde levels were determined. Prior to the ethanol intake and at each sampling of the blood, the pain thresholds were measured by three stimulating methods, i.e., a mechanical method (algometer), a thermal method (Nakahama's pain meter NYT-5) and a chemical method (potassium iontophoretic meter). In the ALDH2*1/*1 and ALDH2*1/*2 groups, the pain threshold measured by the three methods increased with the elevation of blood ethanol levels, especially the threshold by the mechanical method showed clear rise with blood ethanol level. The subjects who belonged to the ALDH2*2/*2 group showed a high blood acetaldehyde level and various psychophysical symptoms. The results of the three tests had no relationships with the variation of blood ethanol levels.

Adult↗
PubMed1993

[Genotypes of alcohol dehydrogenase and aldehyde dehydrogenase and their significance for alcohol sensitivity].

Genotypes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) loci were determined, using allele specific oligonucleotides. Gene frequencies of ADH2(1) and ADH2(2) were 0.29 and 0.71, respectively, in the Japanese control group. No significant difference was found in the ADH2 genotype between the patients and the control group. Gene frequency of ALDH2(1) and ALDH2(2) were 0.65 and 0.35 in the control group, while 0.93 and 0.07, respectively in the patient group. Most of the patients, 20 out of 23, were homozygous Caucasian type. All individuals with homozygous atypical ALDH2(2)/ALDH2(2) and most of those with heterozygous atypical ALDH2(1)/ALDH2(1) were alcohol flushers, while all of the usual ALDH2(1)/ALDH2(1) were nonflushers. The results indicate that Japanese with the atypical ALDH2(2) allele are at a much lower risk in developing alcoholic liver disease than those with usual ALDH2(1)/ALDH2(1), presumably due to their sensitivity to alcohol intoxication.

Alcohol Dehydrogenase↗
PubMed1994

Polymorphisms of ethanol metabolizing enzyme genes and alcoholism.

This study is intended to establish the genotype patterns at the ADH2, ADH3, and ALDH2 loci using a large number of Japanese alcoholics (n = 655) and controls (n = 461) representative of the Japanese general population. It complements an earlier small study and establishes definitively the effects of combinations of the genetic variations of the ADH2 and ADH3 alleles as well as ALDH2, thus providing a precise estimate of the risk for alcoholism. In this study, the alleles ADH2(2), ADH3(1), and ALDH2(2) appeared less frequently in alcoholics than in the general population (p < 0.001). The ADH2(3) allele was not found among 200 alcoholics and 200 controls screened, suggesting that it does not exist in indigenous Japanese. The ADH2(1)/ADH2(2) polymorphism was in linkage disequilibrium with the ADH3(1)/ADH3(2) polymorphism. The haplotype frequencies of ADH2 and ADH3 genes were estimated in the Japanese general and alcoholic populations. Increased risk for alcoholism was shown in individuals with homozygous ALDH2(1) and the ADH2(1) allele (p < 0.001), but the relative risk was less than 1 in those with the homozygous ADH2(2). Japanese with ALDH2(1)/2(2) had a low risk in the presence of the ADH2(2) (p < 0.001), but the risk was significantly increased in those with the homozygous ADH2(1) allele (OR 2.0, 95% CI 1.0-4.3, p < 0.05). The ALDH2(2)/2(2) genotype was found in none of the alcoholics, suggesting that individuals with homozygous ALDH2(2) never become alcoholics.

Adult↗
PubMed1997

Polymorphism of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men.

Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P-450IIEI. The purpose of this study was to clarify the role of polymorphism of these ethanol-metabolizing enzymes in drinking behavior and the progression of alcoholic liver disease among Japanese men. Polymorphism of the ADH2, ALDH2, and P-45IIEI genes were determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis in 189 normal Japanese men and 26 male patients with alcoholic liver disease. Drinking behavior was estimated by self-assessment according to DSM-III-R criteria. Facial flushing was reported in 91 subjects heterozygous for ALDH2*1/*2 and in two subjects homozygous for ALDH2*2/*2, but was not found in 96 subjects homozygous for ALDH2*1/*1. In contrast, polymorphism of ADH2 and P-450IIEI did not differ between flushers and nonflushers. Although the flushers only drank a small amount of alcohol (< 20 g of ethanol/day), the nonflushers were divided into a group of moderate drinkers (20 to 80 g/day; n = 54) and a group of heavy drinkers (> 80 g/day; n = 42). A high preponderance of heterozygosity for the ADH2*1/*2 genes (20/42; 60%) and a high frequency of the ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers. However, cytochrome P-45IIEI gene polymorphism was similar among the moderate and heavy drinkers. Not only a high frequency of the ALDH2*1 and ADH2*1 alleles, but also a high frequency of the P-450IIEI c2 allele was found in the patients with alcoholic liver disease. From these results, the drinking behavior of Japanese men is strongly influenced by the ALDH2*1 allele, and the level of alcohol intake is affected by the ADH2*1 allele, but not by cytochrome P-45IIEI. However, progression to alcoholic liver disease among heavy drinkers may be affected by the cytochrome P-450IIEI c2 allele.

Adult↗
PubMed1997

Reliability of a flushing questionnaire and the ethanol patch test in screening for inactive aldehyde dehydrogenase-2 and alcohol-related cancer risk.

Molecular epidemiology of esophageal and upper aerodigestive tract cancers revealed that alcohol is more carcinogenic in persons with inactive aldehyde dehydrogenase-2 (ALDH2) than in those with active ALDH2. A simple questionnaire has been developed to screen for the facial flushing that occurs in persons with inactive ALDH2 when they drink even a single glass of beer. In this study, 266 of 284 consecutive male Japanese clinic patients (age > or = 50 years) completed the flushing questionnaire, and 239 underwent the ethanol patch test (a cutaneous model for the flushing response). Blinded genotyping showed inactive ALDH2 for 94.4% (102 of 108) of subjects who reported always flushing (early in their drinking history or currently) and for 47.7% (21 of 44) of those who reported sometimes flushing, whereas 95.6% (109 of 114) of subjects reporting that they never exhibited facial flushing had active ALDH2. When all three categories of flushing (current always, former always, and sometimes) were collapsed into one, the questionnaire's sensitivity and specificity for identifying inactive ALDH2 were 96.1 and 79.0%, respectively, compared with 72.4 and 71.4% for the ethanol patch test. 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.

Aged↗
PubMed1996

Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics.

BACKGROUND: Multiple intraesophageal primary cancer and upper aerodigestive tract (UADT) cancer associated with esophageal cancer are common diseases, especially in heavy drinkers. They are often explained by the concept of field cancerization, which suggests a similar etiology. However, little is known about the nature of the hypothesized etiology. METHODS: Among 901 Japanese male alcoholics systematically screened by upper gastrointestinal endoscopy (with esophageal iodine staining), 33 had squamous cell carcinoma of the esophagus. The multiplicity of their esophageal carcinoma and their concurrent UADT cancer was compared with their genotype for aldehyde dehydrogenase-2 (ALDH2), the major determinant of blood acetaldehyde concentration after drinking. RESULTS: Of 17 patients with inactive ALDH2, 13 (76.5%) had multiple primary carcinoma of the esophagus, whereas 5 of 16 (31.3%) with active ALDH2 had multiple carcinomas (P < 0.01). The prevalence of concurrent UADT cancer was 29.4% in those patients with inactive ALDH2, compared with 6.3% in those patients with active ALDH2. CONCLUSIONS: Inactive ALDH2 is a risk factor for multiple carcinoma of the esophagus in alcoholics. Acetaldehyde, a recognized animal carcinogen, appears to play a critical role in field cancerization.

Alcoholism↗
PubMed2005

Mitochondrial aldehyde dehydrogenase polymorphism is not associated with incidence of Alzheimer's disease.

BACKGROUND: The association between the mutant allele of mitochondrial aldehyde dehydrogenase (ALDH2*2) and Alzheimer's disease (AD) has been controversial and only so far investigated in cross-sectional studies. This study aimed to investigate the longitudinal association between ALDH2*2 and incidence of AD. METHODS: Of 592 participants aged 65 or over without dementia at baseline, 510 (86%) were re-evaluated after 2.4 years and comprised the study sample. Baseline measures included: demographic characteristics, drinking behavior, cognitive function (MMSE), clinical diagnoses of dementia and AD, and genotype (ALDH2 and apolipoprotein E). At the follow up examination, alcohol related characteristics, MMSE and clinical diagnoses of dementia and AD were reassessed. RESULTS: There were no significant associations between the ALDH2*2 and any cognitive outcomes (incidence of dementia or AD, or cognitive decline). These findings were not changed after adjustment for alcohol consumption. No interaction was found between ALDH2 and apolipoprotein E. CONCLUSIONS: ALDH2*2 does not seem to be important in the etiology of dementia.

Aged↗
PubMed1997

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients.

It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.

Acute Disease↗
PubMed1985

Enzymatic activity of atypical Oriental types of aldehyde dehydrogenases.

Catalytic activity of the atypical Oriental-type aldehyde dehydrogenase-2 (ALDH2) was considered to be null or severely diminished. Recently it was suggested that the atypical ALDH2(2) retained about 30% of the specific activity of the usual ALDH2(1). We reexamined the problem by two-dimensional crossed immunoelectrophoresis. The usual Caucasian livers exhibited two distinctive precipitin peaks, one corresponding to the cytosolic ALDH1 and the other corresponding to the usual mitochondrial ALDH2(1), in both protein stain and enzyme activity stain. In contrast, the atypical Oriental livers exhibited two precipitin peaks in protein stain, but only one peak, corresponding to ALDH1, in enzyme activity stain. These results support the original notion that the atypical ALDH2(2) is enzymatically inactive or far less active than the usual enzyme, refuting the idea of the atypical ALDH2(2) with substantial enzyme activity.

Aldehyde Dehydrogenase↗
PubMed1993

Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism.

The alcohol-flush reaction occurs in Asians who inherit the mutant ALDH2*2 allele that produces an inactive aldehyde dehydrogenase enzyme. In these individuals, high blood acetaldehyde levels are believed to be the cause of the unpleasant symptoms that follow drinking. We measured the alcohol elimination rates and intensity of flushing in Chinese subjects in whom the alcohol dehydrogenase ADH2 and ALDH2 genotypes were determined. We also correlated ADH2, ADH3, and ALDH2 genotypes with drinking behavior in 100 Chinese men. We discovered that ADH2*2 and ADH3*1, alleles that encode the high activity forms of alcohol dehydrogenase, as well as the mutant ALDH2*2 allele were less frequent in alcoholics than in controls. The presence of ALDH2*2 was associated with slower alcohol metabolism and the most intense flushing. 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.

Alcohol Dehydrogenase↗
PubMed1995

Alcohol consumption by orientals in North America is predicted largely by a single gene.

Orientals consume significantly less alcohol, and show a lower prevalence of alcohol abuse and dependence, than Caucasians. Sociological theories propose that this difference is due mainly to cultural factors. Physiological theories have suggested that the flushing reaction experienced by some Orientals serves as a deterrent to ethanol consumption. The flushing reaction is observed mainly in individuals who possess a mutation in the high-affinity aldehyde dehydrogenase (ALDH2) which renders the enzyme inactive. However, the tendency to flush correlates poorly with alcohol consumption, thus casting doubt on the physiological interpretations. The present study investigates the influence of the ALDH2 allele and of acculturation in North America on alcohol consumption by Orientals born in Canada or the United States. Oriental males carrying the inactive ALDH2(-) allele drink two-thirds less alcohol (6.1 +/- 1.5 vs. 18.2 +/- 2.8 drinks/4 weeks; p < 0.001), show one-third the prevalence of binge drinking (15.2 vs. 42.2%; p < 0.01), and are three times more likely to be abstainers (39.4 vs. 13.3%; p < 0.01) than Oriental ALDH2(+) males carrying the gene for the active enzyme. There were no significant differences in binge drinking or abstinence rates between ALDH2(+) Orientals and Caucasian males. Acculturation in North American society accounted for only 7-11% of the variance in overall consumption (p < 0.02). It is concluded that a single mutation in the high-affinity aldehyde dehydrogenase (ALDH2) gene predicts two-thirds of the alcohol consumption and excessive alcohol use by Oriental males born in North America.

Acculturation↗
PubMed1996

The contribution of polymorphism in the alcohol dehydrogenase beta subunit to alcohol sensitivity in a Japanese population.

In humans, ingested alcohol is mainly metabolized by the combination of class I alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). In Orientals, there are highly frequent polymorphisms both in the class I ADH beta subunit (ADH2) and in the low Km ALDH (ALDH2). We characterized the three genotypes of ALDH2 in a Japanese population. In the present study, we evaluated the effects of the ADH2 polymorphism in the same population (424 males and 100 females) controlling for the effects of the ALDH2 polymorphism. 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. Likewise, the proportion of persons with positive results for ethanol-induced cutaneous erythema differed significantly depending on the ADH2 genotype in both the ALDH2(1)/ALDH2(1) and ALDH2(1)/ALDH2(2) genotypes. However, drinking habits were not significantly associated with the ADH2 genotype, suggesting that the ADH2 genotype influences the metabolism of ethanol only in the peripheral tissues.

Adult↗
PubMedDate not supplied

Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.

Usual human livers contain two major ALDH isozymes, i.e., cytosolic ALDH1 and mitochondrial ALDH2, while approximately 50% of Orientals are "atypical" and have only the ALDH1 and are missing the ALDH2. Instead, the atypical livers contain an enzymatically inactive but immunologically cross-reactive material (CRM) corresponding to the ALDH2 component. Some Orientals are found to be atypical also in the ALDH1 locus, i.e., they are missing the enzymatically active ALDH1 but contain a large amount of CRM corresponding to the ALDH1 component. cDNA for ALDH1 and that for ALDH2 were cloned and their nucleotide sequences were determined. The amino acid sequences of ALDH1 and ALDH2 were deduced from their cDNA sequences. The molecular abnormality of the inactive ALDH2(2) is found to be the substitution of Glu at the 14th position from the COOH-terminal of the protein by Lys which resulted from G----A transition in the gene.

Aldehyde Dehydrogenase↗
PubMed2004

Association of aldehyde dehydrogenase-2 polymorphism with alcoholic polyneuropathy in humans.

Persons who have the Glu-487-->Lys mutation (single nucleotide polymorphism) of the aldehyde dehydrogenase-2 (ALDH2) gene have less ability to metabolize the alcohol breakdown product acetaldehyde. In order to clarify whether acetaldehyde is associated with the pathogenesis of alcoholic polyneuropathy, we compared nerve conduction data as well as clinical signs and symptoms of neuropathy between alcoholics with ALDH2*2 (Lys-487) heterozygotes and those with ALDH2*1 (Glu-487) homozygotes. Alcoholics with ALDH2*2 heterozygotes showed significantly lower sensory nerve action potential amplitudes of the sural and median nerves than those with ALDH2*1 homozygotes, suggesting that the accumulation of acetaldehyde due to ALDH2 inactivity is associated with alcoholic polyneuropathy.

Action Potentials↗
PubMed2006

Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal.

Recent evidence indicates a role for oxidative stress and resulting products, e.g. 4-hydroxy-2-nonenal (4HNE) in the pathogenesis of Parkinson's disease (PD). 4HNE is a known inhibitor of mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme very important to the dopamine (DA) metabolic pathway. DA undergoes monoamine oxidase-catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4-dihydroxyphenylacetic acid (DOPAC) via ALDH2. The biotransformation of DOPAL is critical as previous studies have demonstrated this DA-derived aldehyde to be a reactive electrophile and toxic to dopaminergic cells. Therefore, 4HNE produced via oxidative stress may inhibit ALDH2-mediated oxidation of the endogenous neurotoxin DOPAL. To test this hypothesis, ALDH2 in various model systems was treated with 4HNE and activity toward DOPAL measured. Incubation of human recombinant ALDH2 with 4HNE (1.5-30 microM) yielded inhibition of activity toward DOPAL. Furthermore, ALDH2 in rat brain mitochondrial lysate as well as isolated rat brain mitochondria was also sensitive to the lipid peroxidation product at low micromolar, as evident by a decrease in the rate of DOPAL to DOPAC conversion measured using HPLC. Taken together, these data indicate that 4HNE at low micromolar inhibits mitochondrial biotransformation of DOPAL to DOPAC, and generation of the lipid peroxidation product may represent a mechanism yielding aberrant levels of DOPAL, thus linking oxidative stress to the uncontrolled production of an endogenous neurotoxin relevant to PD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2005

Effects of alcohol on hemodynamic and cardiovascular reaction in different genotypes.

This study assessed hemodynamic changes associated with alcohol intake in people who have different sensitivities to alcohol due to an inactive form of mitochondrial aldehyde dehydrogenase (ALDH). People with ALDH2*1/*2 are more sensitive to alcohol than people with ALDH2*1/*1. Six ALDH2*1/*1 subjects and four ALDH2*1/*2 subjects participated in this study. The subjects drank whisky with water (0.4 ml/kg of ethanol). Optical topography (Hitachi Medical Corporation: ETG-100) was used to measure hemodynamic changes in an occipital region during visual stimulation. Hemodynamic changes, heart rate, mean blood pressure, and reaction time were measured 20 min before, immediately after, and 20, 40, and 60 min after alcohol intake. Breath-alcohol concentration was measured at each of the assessment points. After alcohol intake, the hemodynamic peak value, peak time, reaction time, and heart rate of the ALDH2*1/*2 subjects differed from those of the ALDH2*1/*1 subjects. The hemodynamic peak value and reaction time gradually increased 60 min after alcohol exposure, and the peak time was shortest 20 min after alcohol intake. These results might reflect different acetaldehyde levels causing changes in the reactivity of the vascular smooth muscle and cerebral activity in the visual cortex.

Aldehyde Dehydrogenase↗
PubMed1999

S-methyl N-butylthiocarbamate sulfoxide: selective carbamoylating agent for mouse mitochondrial aldehyde dehydrogenase.

Liver mitochondrial low-Km aldehyde dehydrogenase (ALDH2, EC 1.2.1.3), the isoform responsible for the conversion of acetaldehyde to acetate, is inhibited by the sulfoxide bioactivation products of Et2NC(O)SMe (from the alcohol aversion drug disulfiram), Pr2NC(O)SEt (the herbicide S-ethyl N,N-dipropylthiocarbamate), and BuNHC(O)SMe (from the fungicide benomyl). This study tested the hypothesis that bioactivated BuNHC(O)SMe, the most potent of these thiocarbamates, is a selective carbamoylating agent for ALDH2 of mouse liver in vivo and in vitro. [14C]BuNHC(O)SMe administered i.p. to mice labeled one principal mitochondrial protein, which cochromatographed with ALDH activity by in-gel assay after isoelectric focusing. The labeled protein was isolated by isoelectric focusing (pI 6.1) and SDS-PAGE (54 kDa) and identified as ALDH2 by sequencing of peptides from a tryptic digest. In vivo at 1.5 mg/kg, enzyme inhibition was 80%, and ALDH2 was the only mitochondrial protein labeled extensively, illustrating the outstanding potency and specificity. ALDH2 also was labeled upon incubation of mouse liver mitochondria with [14C]BuNH-C(O)SMe in the presence of microsomes (P450) and NADPH. In contrast, under similar conditions, [14C]Pr2NC(O)SEt sulfoxide labeled primarily two other proteins at approximately 58 and approximately 61 kDa, establishing a very different selectivity for the two sulfoxides. These findings are of interest relative to selective inhibitors and carbamoylating agents for ALDH2 and to alcohol aversion upon exposure to herbicides and fungicides.

Aldehyde Dehydrogenase↗
PubMed2002

Genetic variation in aldehyde dehydrogenase 2 and the effect of alcohol consumption on cholesterol levels.

UNLABELLED: Moderate drinkers with a defective alcohol dehydrogenase type 3 (ADH3) genotype have higher high-density lipoprotein (HDL) levels and a decreased risk of coronary artery disease (CAD). We examined the interaction between the aldehyde dehydrogenase type 2 (ALDH2), alcohol intake, and HDL levels in 826 men and 1295 women in a rural town in Japan. The ALDH2 genotype of each subject was determined by polymerase chain reaction (PCR) analysis. HDL was adjusted for the alcohol intake, age, body mass index, smoking status, total cholesterol, triglycerides and HbA1c levels. None of the subjects had a history or ECG suggestive of CAD. The proportions of ALDH2, *1/*1, *1/*2, and *2/*2 (defective homozygote) were 45.8, 46.0, and 8.2%, respectively, for men. Drinking more than two drinks daily was associated with lower HDL levels in men with the defective genotypes compared with men with a normal genotype (55.6+/-0.9 vs. 51.2+/-0.9 mg/dl, mean+/-S.E., P<0.0001). Also, drinking more than 0.5 drinks daily was not associated with beneficial effects on HDL levels in women with defective ALDH2 genotypes. CONCLUSIONS: Alcohol intake did not have beneficial effects on HDL levels in the defective ALDH2 genotype and may not protect against CAD in subjects with defective ALDH2 genotypes.

Adult↗