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PubMed2003

Development and evaluation of an automated workstation for single nucleotide polymorphism discrimination using bacterial magnetic particles.

We designed an automated workstation for magnetic particle-based single nucleotide polymorphism (SNP) discrimination of ALDH genotypes. Bacterial magnetic particles (BMPs) extracted from Magnetospirillum magneticum AMB-1 were used as DNA carriers. The principle for SNP discrimination in this study was based on fluorescence resonance energy transfer (FRET) between FITC (donor) and POPO-3 (acceptor) bound to double-stranded DNA. The workstation is equipped with a 96-way automated pipetter which collects and dispenses fluids as it moves in x- and z-directions. The platform contains a disposable tip rack station, a reagent vessel serving as a stock for POPO-3 and FITC-labeled probes and a reaction station for a 96-well microtiter plate. BMPs were collected by attaching a neodymium iron boron sintered (Nd-Fe-B) magnet on the bottom of the microtiter plate. This system permits the simultaneous heating and magnetic separation of 96 samples per assay. The genotypes ALDH2*1 and ALDH2*2 were discriminated by calculating the relative fluorescence intensities on BMPs.

Aldehyde Dehydrogenase↗
PubMed2006

Inhibition of human mitochondrial aldehyde dehydrogenase by 4-hydroxynon-2-enal and 4-oxonon-2-enal.

Previous studies found the lipid peroxidation product 4-hydroxynon-2-enal (4HNE) to be both a substrate and an inhibitor of mitochondrial aldehyde dehydrogenase (ALDH2). Inhibition of the enzyme by 4HNE was demonstrated kinetically to be reversible at low micromolar aldehyde but may involve covalent modification at higher concentrations. Structurally analogous to 4HNE is the lipid peroxidation product 4-oxonon-2-enal (4ONE), which is more reactive than 4HNE toward protein nucleophiles. The goal of this work was to determine whether 4ONE is a substrate or inhibitor of human ALDH2 (hALDH2) and elucidate the mechanism of enzyme inhibition by 4HNE and 4ONE. Both 4ONE and its glutathione conjugate were found to be substrates for the enzyme in the presence of NAD. At low concentrations of 4ONE (< or = 10 microM), hALDH2 catalyzed the oxidation of 4ONE to 4-oxonon-2-enoic acid (4ONEA) with a maximal yield of 5.2 mol 4ONEA produced per mol of enzyme (monomer). However, subsequent analysis of hALDH2 activity toward propionaldehyde revealed that both 4ONE and the oxidation product, 4ONEA, were potent, irreversible inhibitors of the enzyme. In contrast, inhibition of hALDH2 by a high concentration of 4HNE (i.e., 50 microM) was primarily reversible. The reactivity of 4ONEA toward glutathione was measured and found to be comparable to that of 4HNE, indicating that the 4ONE-oxidation product is a reactive electrophile. hALDH2/NAD was incubated with 4HNE, 4ONE, and 4ONEA, and mass spectral analysis of tryptic peptides revealed covalent modification of an hALDH2 active site peptide by both 4ONE and 4ONEA. These data demonstrate that hALDH2 catalyzes the oxidation of 4ONE to 4ONEA; however, the product 4ONEA is a reactive electrophile. Furthermore, both 4ONE and 4ONEA are potent, irreversible inhibitors of the enzyme.

Aldehyde Dehydrogenase↗
PubMed2002

Contribution of genetic polymorphisms in ethanol-metabolizing enzymes to problem drinking behavior in middle-aged Japanese men.

Among ethanol-metabolizing enzymes, the ALDH2*2 allele, ADH2*2 allele, and c2 allele of the cytochrome P450-2E1 (CYP2E1) gene are unique to Orientals. This prompted us to analyze their contribution to drinking behavior in 322 middle-aged Japanese men. The ALDH2*2 allele, detected in nearly half of the subjects, showed an overwhelming protective effect against a high level of alcohol consumption and problem drinking behavior, as determined by the Kurihama Alcoholism Screening Test (KAST). The ADH2*2 allele, in 95% of the subjects, exhibited an additive suppressive effect on alcohol consumption, whereas the c2 allele of CYP2E1, in 40% of the subjects, was associated with greater alcohol consumption. Problem drinkers showing a KAST score of 2.0 or higher were frequent among the few subjects with the ADH2*1/1 genotype, but not in the large number of subjects having the c2 allele of CYP2E1. These findings may explain, at least in part, why in Japan the number of alcoholic patients is small relative to the number of heavy drinkers.

Adult↗
PubMed2002

Polymorphism in alcohol-metabolizing enzymes, glutathione S-transferases and apolipoprotein E and susceptibility to alcohol-induced cirrhosis and chronic pancreatitis.

BACKGROUND AND AIM: Susceptibility to organ damage induced by alcohol may be due to inherited variation (polymorphism) in ethanol-metabolizing enzymes, or to polymorphisms affecting free radical or lipid metabolism mediated by enzymes such as glutathione S-transferases and apolipoprotein E. The aim was to compare the genotype frequencies of alcohol dehydrogenase-2 (ADH2), ADH3, aldehyde dehydrogenase-2 (ALDH2), cytochrome P450-2E1 (CYP2E1), glutathione S-transferase-M1 (GSTM1), GSTT1, and apolipoprotein E in patients with alcoholic cirrhosis and alcoholic chronic pancreatitis to those in control groups. PATIENTS AND METHODS: The case-control study was restricted to Caucasian adults: 57 with alcoholic cirrhosis, 71 with alcoholic chronic pancreatitis, 57 alcoholics without apparent organ damage and 200 healthy blood donors. Genotypes were determined by restriction fragment length polymorphism after amplification of genomic DNA by polymerase chain reaction. RESULTS: The genotype ADH3*2/*2 was more frequent in patients with cirrhosis (40%) than blood donors (12%; OR 4.92, 95% CI 2.36-10.31) and patients with chronic pancreatitis (8%; OR 7.33, 95% CI 2.54-23.78) but was not significantly different from alcoholic controls (23%; OR 2.27, 95% CI 0.95-5.66). Patients with cirrhosis also had a higher frequency (P < 0.05) of ADH2*1/*1 (100%) than blood donors (92%) and those with chronic pancreatitis (93%). The frequencies of genotypes of ALDH2, CYP2E1, GSTM1, GSTT1 and apolipoprotein E were similar in all groups. CONCLUSION: Alcoholic cirrhosis but not alcoholic chronic pancreatitis is associated with ADH3*2/*2 and perhaps with ADH2*1/*1. Both genes encode less active alcohol-metabolizing enzymes that may be associated with cirrhosis because of delayed formation of acetaldehyde (with higher intakes of alcohol), or diversion of alcohol metabolism through pathways other than ADH.

Adult↗
PubMed1997

Human stomach alcohol and aldehyde dehydrogenases: comparison of expression pattern and activities in alimentary tract.

BACKGROUND & AIMS: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. The human stomach has been documented to be involved in the metabolism of first-passed alcohol. The aim of this study was to determine ethanol-metabolizing activities in the stomach with regard to sex, age, enzyme pattern, and polymorphism. METHODS: A total of 209 surgical gastric mucosal specimens were investigated. The expression patterns of ADH and ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. RESULTS: At 33 or 500 mmol/L ethanol, pH 7.5, the activities in the ADH3 1-1 phenotypic and mu-ADH-expressing mucosal specimens were significantly greater than that in the ADH3 1-2 phenotypic and mu-ADH absent mucosal specimens, respectively. The activities of the ALDH2-inactive phenotypes were significantly lower than that of the ALDH2-active phenotypes at 200 micromol/L acetaldehyde. The gastric ADH and ALDH activities were not significantly different between men and women with respect to age and genetic polymorphism. CONCLUSIONS: The stomach may contribute only a small portion of the alcohol metabolism observed in humans, and the liver may be the major site for first-pass metabolism. Differential expression patterns of ADH and ALDH in the alimentary tract suggest that different vulnerabilities to ethanol-induced mucosal injury may exist.

Adult↗
PubMed1996

Heterotetramers of human liver mitochondrial (class 2) aldehyde dehydrogenase expressed in Escherichia coli. A model to study the heterotetramers expected to be found in Oriental people.

About 50% of the Oriental population have less liver mitochondrial aldehyde dehydrogenase (ALDH2) activity than do other people. It was found that they possessed an enzyme with a lysine at position 487 (E487K) instead of glutamate (Glu487). We previously found that the Km for NAD of recombinant human and rat E487K enzymes increased more than 150-fold (Farrés, J., Wang X., Takahashi, K., Cunningham, S. J. , Wang, T.T., and Weiner, H (1994) J. Biol. Chem. 269, 13854-13860). Many aldehyde dehydrogenase-deficient people were found to be heterozygous when genotyped for ALDH2. In this study liver tissue from heterozygous people was analyzed and found to possess mRNAs for both the glutamate and the lysine subunits. Western blot analysis showed that the glutamate subunit was present. The cDNAs for Glu487 and E487K were coexpressed on one plasmid in Escherichia coli, and the enzyme forms were separated from each other by isoelectric focusing to show that heterotetramers were formed. Only one Km value for NAD could be measured with the purified heterotetrameric enzyme that possessed just 16-18% activity of the glutamate homotetrameric enzyme. The E487K homotetramers had 8% specific activity of the Glu487 enzyme. There was no pre-steady state burst of NADH formation with the heterotetramer, a property found with the glutamate enzyme. Similar results were found for the coexpressed rat liver enzyme, except that a higher specific activity, 48%, was obtained. Thus, we conclude that presence of the lysine subunit altered the activity of the glutamate subunit in the heterotetramer to make it function more like an E487K enzyme.

Aldehyde Dehydrogenase↗
PubMed2003

Simultaneous genotyping of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 by single-strand conformation polymorphism analysis.

Alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) have important roles in the elimination of ingested ethanol. These enzymes have polymorphisms resulting from single-point mutations that cause kinetic differences in their respective enzyme activities. Simultaneous observation of these enzymes would be useful in investigating the association between these enzyme polymorphisms and alcohol-related problems. In this study amplified genomic DNA was amplified from nail clippings with two sets of primers for ADH2 and ALDH2 genes, respectively, in a micro test tube and the accuracy of the amplification was verified by direct sequencing. The PCR products were separated into four distinct bands by single-strand conformation polymorphism analysis. This genotyping method is fast, accurate. reliable and inexpensive, and requires the same amount of template DNA as non-simultaneous methods. In other words, the required amount of template DNA for this method is only half that required for the separate genotyping of ADH2 and ALDH2.

Alcohol Dehydrogenase↗
PubMed1993

Role of the aldehyde dehydrogenase-1 isozyme in the metabolism of acetaldehyde.

At least four types of aldehyde dehydrogenase (ALDH) isozymes exist in human liver: acetaldehyde (Ac-CHO) is metabolized mainly by ALDH2. However, the role of ALDH1 in Ac-CHO metabolism is not well known, because ALDH1 deficiency is rare. In the present study, changes in blood levels of Ac-CHO were analyzed in a person with ALDH1 deficiency who is also heterozygous for the ALDH2 alleles, and subjects with normal ALDH1, in order to clarify the roles of ALDH1 in the metabolism of Ac-CHO. By isoelectric focusing analysis of ALDH in red blood cells (RBC), the ALDH1 band was not detectable in a male subject, indicating ALDH1 deficiency. In this subject, ALDH1 activity was nearly null, but the activities in his wife and two children were normal. Serial changes of blood Ac-CHO levels following a small amount of ethanol were analyzed. The peak levels of Ac-CHO were not different between the subject with ALDH1 deficiency and the person with normal ALDH1. However, the decrease from the peak values of Ac-CHO was clearly slower in the deficient subject than in ALDH1 normal subjects. Changes in Ac-CHO in blood were also analyzed in vitro. Ac-CHO metabolism by RBC from the ALDH1 deficient subjects was clearly slower than in those from controls. These results indicate that ALDH1 plays an important role in the metabolism of Ac-CHO in blood.

Acetaldehyde↗
PubMedDate not supplied

Association of cholecystokinin-A receptor gene polymorphism with alcohol dependence in a Japanese population.

AIMS: Cholecystokinin (CCK), one of the most abundant neurotransmitter peptides, interacts with dopamine. Dopaminergic neurotransmission between the ventral tegmental area and the limbic forebrain is a critical neurobiological component of alcohol and drug self-administration. CCK modulates dopamine release in the nucleus accumbens via the CCK-A receptor (R). We recently determined the transcriptional start site of the human CCK-AR gene, and detected two sequence changes (-81A/G and -128G/T) in the promoter region. The aims of the present study were to determine the prevalence of the -81A/G and -128G/T polymorphism of the CCK-AR gene between alcoholics and normal control subjects and the occurrences of the polymorphisms in subtypes of alcoholics. METHODS: The above polymorphisms were examined in 435 alcoholics and 1490 control subjects. We excluded subjects with inactive ALDH2 and employed the subjects with ALDH2*1/2*1 (384 alcoholics and 792 controls). RESULTS: The allelic frequency of -81G in the CCK-AR gene polymorphism (-81A/G) was significantly higher in alcoholics than in control subjects. However, there were no differences between the two groups with respect to the frequency of -128G/T. Alcoholic patients with antisocial personality disorder and with first-degree alcoholic relatives were significantly associated with a higher frequency of the -81G allele. In addition, the age of onset of alcohol dependence was significantly earlier in patients with this allele. CONCLUSIONS: The CCK-AR gene -81A/G polymorphism, especially in the -81G allele, may be associated with intractable alcoholism.

Adult↗
PubMed2006

Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder.

AIMS: To examine the clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder (ADHD). METHODS: The present study included 85 male alcoholics who were diagnosed as having DSM-IV alcohol dependence. A total of 28 (32.9%) alcoholics were diagnosed as having DSM-IV ADHD with ongoing symptoms in adulthood. For the evaluation of their psychiatric conditions, the alcohol dependence scale (ADS), Beck depression inventory (BDI), Beck anxiety inventory (BAI), Barratt impulsiveness scale (BIS), brief anger-aggression questionnaire (BAQ), overt aggression scale (OAS), codependence test, and obsessive compulsive drinking scale (OCDS) were administered. The genotype frequencies of the dopamine type 2 receptor gene (DRD2), aldehyde dehydrogenase type 2 gene (ALDH2), functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR), and catechol-O-methyltransferase gene (COMT) polymorphisms were examined. RESULTS: Compared with alcoholics without ADHD, the mean ages for the onset of pathological drinking and alcohol withdrawal hallucinations were significantly earlier in alcoholics with ADHD. There was also a significant difference in the history of antisocial behaviour between the two groups. Compared with alcoholics without ADHD, the mean scores of the ADS, BDI, BAI, OAS, and OCDS were significantly higher in alcoholics with ADHD. With regard to the codependence test results, the mean scores of the interpersonal problem, low self-esteem and anxiety/fear subscales, and the mean total score of the codependence test were significantly higher in alcoholics with ADHD when compared with those without ADHD. There were no significant differences in the genotype frequencies of the DRD2, ALDH2, 5-HTTLPR, and COMT polymorphisms between alcoholics with and without ADHD. CONCLUSIONS: The results of this study suggest that the comorbidity of alcohol dependence and ADHD in this Korean sample forms a distinct clinical phenotype that shows an increased severity of alcohol-related symptoms and behavioural/emotional problems and that ADHD is associated with an increased risk for the early onset of alcohol dependence in Korean male alcoholics.

Adult↗
PubMed2004

Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies.

A growing body of evidence implicates alcohol intake as a risk factor for colorectal cancer. Until recently, most of the data were based on epidemiologic data that examined alcohol intake in relation to risk of colorectal neoplasia, but the evidence has now been broadened by recent molecular studies on mechanisms. In particular, a number of observations strongly support a role for alcohol acting through disruptions in one-carbon metabolism. Excessive alcohol intake is a fairly consistent risk factor for colorectal neoplasia in most studies, and studies show much higher risks of colorectal neoplasia in those with high alcohol and low folate than with high alcohol or low folate individually. Interactions between high alcohol-low folate and the MTHFR677TT genotype with risk of colorectal neoplasia suggest that alcohol is acting through its effects on one-carbon metabolism because the combination of high alcohol-low folate and the MTHFR677TT genotype are related to markedly elevated serum levels of homocysteine and to DNA hypomethylation. In addition, in Japanese studies, consumers of alcohol possessing the ALDH2*2 allele, who have very elevated levels of acetaldehyde, are at high risk for colorectal cancer. The relatively high prevalence of the ALDH2*2 allele may thus account for the stronger association between alcohol and colorectal neoplasia that is frequently observed in studies in Japanese populations. Further research integrating studies with more detailed data on alcohol intake levels and patterns, folate and other related nutrient status, and relevant genotypes may help clarify unresolved questions regarding the health consequences of moderate to high alcohol drinking.

Alcohol Drinking↗
PubMed1989

Hepatic lipid peroxidation and aldehyde dehydrogenase activity in alcoholic and non alcoholic liver disease.

It has been suggested that lipid peroxidation plays a role in the pathogenesis of chronic alcoholic liver disease (CALD). However, whether or not CALD differs from chronic non alcoholic liver disease (CLD) in lipid peroxidation, is still questionable. Thirty-eight patients affected by CALD and CLD who were matched for age, sex, nutrition and liver function tests (LFTs) and 17 controls (C) took part in this study. The following tests were performed: serum and liver malondialdehyde (MDA) determination by the TBA test, liver total glutathione (GSH) estimate, mitochondrial (ALDH2) and cytosolic (ALDH1) aldehyde dehydrogenase activity determinations. Patients who showed signs of malnutrition were excluded from this study. Serum and hepatic TBA-reactive substances resulted in a slight increase in chronic liver patients compared to controls but did not show any difference between CALD and CLD groups. Liver total glutathione did not show any change. Hepatic ALDH2 activity was significantly (P less than 0.01) higher in CALD than in CLD and control patients whereas ALDH1 did not show any difference. These results suggest that the increased lipid peroxidation in CALD and in CLD is probably secondary to liver damage rather than being the pathogenic factor.

Adult↗
PubMed2005

Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver and lung development.

Metabolism is one of the major determinants for age-related changes in susceptibility to chemicals. Aldehydes are highly reactive molecules present in the environment that also can be produced during biotransformation of xenobiotics and endogenous metabolism. Although the lung is a major target for aldehyde toxicity, early development of aldehyde dehydrogenases (ALDHs) in lung has been poorly studied. The expression of ALDH in liver and lung across ages (postnatal day 1, 8, 22, and 60) was investigated in Wistar-Han rats. In adult, the majority of hepatic ALDH activity was found in mitochondria, while cytosolic ALDH activity was the highest contributor in lung. Total aldehyde oxidation capability in liver increases with age, but stays constant in lung. These overall developmental profiles of ALDH expression in a tissue appear to be determined by the different composition of ALDH isoforms within the tissue and their independent temporal and tissue-specific development. ALDH2 showed the most notable tissue-specific development. Hepatic ALDH2 was increased with age, while the pulmonary form did not. ALDH1 was at its maximum value at postnatal day 1 (PND1) and decreased thereafter both in liver and lung. ALDH3 increased with age in liver and lung, although ALDH3A1 was only detectible in lung. Collectively, the present study indicates that, in the case of aldehyde exposure, the in vivo responses would be tissue and age dependent.

Aging↗
PubMed2001

Association of polymorphism in the alcohol dehydrogenase 2 gene with alcohol-induced testicular atrophy.

BACKGROUND: Alcohol abuse can induce testicular atrophy, but it only occurs in some alcoholics. Alcohol dehydrogenase (ADH) is located principally on the Leydig cells. METHODS: To investigate whether genetic polymorphism of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 was related to alcoholic testicular atrophy, we determined restriction fragment-length polymorphisms of the ADH2 and ALDH2 genes in 43 Japanese male alcoholics and 50 healthy subjects. An orchidometer was used to determine the testicular size. RESULTS: Less than 16 ml in testicular size was defined as testicular atrophy. Testicular atrophy was found in 24 (55.8%) cases out of 43 alcoholics. Digestion with MaeIII and MboII after polymerase chain reaction amplification showed that the ADH21 allele frequency was significantly higher in patients with testicular atrophy than in those without testicular atrophy (chi2 = 4.665, p = 0.031), whereas no significant association was observed between testicular atrophy and the ALDH2 gene. CONCLUSIONS: The ADH21 allele may be associated with alcoholic testicular atrophy.

Adult↗
PubMed2001

Polymorphism of the neuropeptide Y gene: an association study with alcohol withdrawal.

BACKGROUND: Neuropeptide Y (NPY) exists in both the central and peripheral nervous system and is thought to modulate many functions such as feeding behavior, anxiety-associated behavior, circadian rhythm, seizure modulation, and hormone secretion. Recent studies have revealed that NPY influences alcohol consumption in mice and that alcohol-preferring rats showed lower concentrations of NPY-like immunoreactivity compared with alcohol-nonpreferring rats in several brain regions. METHODS: In the present study, we analyzed the whole coding region and 5'-untranslating region of the NPY gene for 163 Japanese male alcoholics with different withdrawal symptoms (93 with delirium tremens, 71 with seizures, 49 with hallucinations) and 98 Japanese male controls. ALDH2 genotypes of all subjects tested were ALDH2*1 homozygote. RESULTS: Three polymorphic nucleotide substitutions, namely -121C/A (promoter), 1258G/A (exon 2), and 5671C/T (exon 3), were detected in both groups. Substituting C to A in the -121 locus produced a putative binding site of GATA-1 and GATA-2. Also, -90G/A (promoter) as a rare variant and 5642-5651 single nucleotide repeats T10/T11 (intron 2) were found. Polymorphism (C/T) at the 1128 locus has been reported to be associated with a higher serum cholesterol level in obese white subjects, but such a polymorphism was not found in our samples. The genotypical distributions for these polymorphic loci (-121C/A, 1258G/A, 5642-5651 T10/T11, and 5671C/T) were not significantly different between the alcoholics and controls. However, frequency of the T allele and frequency of the genotype that possessed T alleles (CT, TT) at the 5671 locus were significantly higher in patients with seizure than in those without seizure (p < 0.05, p < 0.02). CONCLUSION: Our data suggested that a C to T substitution at the 5671 locus of the NPY gene may be associated with seizure during alcohol withdrawal.

5' Untranslated Regions↗
PubMed1997

Effects of daily alcohol intake on the blood pressure differ depending on an individual's sensitivity to alcohol: oriental flushing as a sign to stop drinking for health reasons.

OBJECTIVE: To determine whether flushing of the facial skin in response to alcohol consumption (alcohol flushing) is a warning sign of hypertension. We also sought the relationship between alcohol flushing and other risk factors that may contribute to the development of hypertension. METHODS: We first investigated the relationship of the aldehyde dehydrogenase 2 (ALDH2) genotype to alcohol flushing for 53 normal volunteers. We evaluated the relationships among hypertension, alcohol consumption, and facial flushing for 1011 middle-aged Japanese men (aged 40-68 years; mean 51.6 +/- 5.5 years), on the basis of their responses to questionnaires and health records. RESULTS: 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). Hypertension was observed in 27.4% of the study population (277 of 1011), and was correlated positively to alcohol consumption (P < 0.01). The prevalence of hypertension differed significantly among these four groups: there was a 22.4% prevalence (70 of 312) among subjects with no flushing, a 33.8% prevalence (113 of 334) among those with slight flushing, a 27% prevalence (84 of 311) among those with visible flushing, and an 18.5% prevalence (10 of 54) among subjects who were almost completely intolerant to alcohol (P < 0.05). In particular, heavy drinkers who consumed > or = 1.5 Go (a traditional Japanese unit equivalent to 27 g ethanol) a day had a high prevalence of hypertension with slight and visible skin flushing [42% (63 of 150) and 40.7% (24 of 59), respectively]. That a family history of hypertension, greater age, heavy alcohol consumption, obesity, and symptoms of intoxication including flushing were correlated significantly to the prevalence of hypertension for all groups was demonstrated by multiple logistic regression analysis (P < 0.05). CONCLUSIONS: A repeated heavy alcohol intake could increase the risk of hypertension for Japanese subjects who exhibit skin flushing in response to alcohol consumption. Chronic alcohol intake by subjects with alcohol flushing might bring about a significant increase in blood acetaldehyde levels and cause an additional rise in the blood pressure.

Adult↗
PubMed1992

Pharmacogenetics of alcohol metabolism and alcoholism.

The pharmacogenetic differences among individuals in their capacity to metabolize ingested alcohol are possibly responsible for the large inter-individual and inter-ethnic variations observed in the outcome of alcohol use and misuse. Based on results of adoption, twin, and family studies it is now widely accepted that the vulnerability to alcoholism is determined by genetic factors as well as by environment. There is a constant search for biological markers and specific genes which could identify individuals genetically predisposed to alcohol abuse and alcoholism. Numerous 'candidate genes' for alcoholism have been suggested including the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both ADH and ALDH exhibit genetic heterogeneity. An atypical form of ADH (ADH2), which contains a variant beta 2 subunit instead of the usual beta 1 subunit, differs substantially from the usual form in its kinetic properties and is found more frequently among the Japanese, Chinese and other Mongoloid populations than in Caucasoids and Negroids. A widely prevalent genetic polymorphism has been observed for ALDH; about 50% of Japanese and Chinese livers possess an inactive ALDH (ALDH2 isozyme) whereas none of the Caucasian or Negroid populations show this isozyme abnormality. These metabolic polymorphisms seem to contribute to differences in the in vivo elimination rate of ethanol and acetaldehyde, and may explain differences in alcohol-related behaviour and its disease outcome. Taken together, Orientals who possess an atypical ALDH2 gene are more sensitive to acute responses to alcohol, tend to be discouraged from drinking alcohol, and consequently are at lower risk of developing alcohol-related disorders. However, more work is needed to support these findings. Recent advances in molecular genetics have made it possible to analyze directly the human genome. This may help in a better understanding of the complex genetic and environmental factors in alcohol abuse by providing prospects for identification of gene loci which may be responsible for predisposition to, and protection from, alcoholism.

Alcohol Dehydrogenase↗
PubMed2003

Neither antisocial personality disorder nor antisocial alcoholism is associated with the MAO-A gene in Han Chinese males.

BACKGROUND: Recent studies on the genetics of alcoholism have suggested an association between antisocial alcoholism and the MAO-A gene. However, previous studies have failed to include subjects with antisocial personality disorder without alcoholism even though there is a high comorbidity between antisocial personality disorder and alcoholism. Consequently, the finding of an association between the MAO-A gene and alcoholism or antisocial personality disorder seems tenuous. In Taiwan, about 70% of the Han Chinese population have the ADH2*2 allele and 50% show ALDH2*1/*2 or ALDH2*2/*2 genotypes, which offer protection against drinking behavior and the risk of developing alcoholism. Thus, it is possible to recruit individuals with antisocial personality disorder but without alcoholism in Taiwan. Therefore, association studies of alcoholism or antisocial personality disorder in Chinese may be more reliable if pure antisocial alcoholics, pure antisocial personality disorders, and normal controls as MAO-A gene are examined. METHODS: In this study, the associations among antisocial alcoholism, antisocial personality disorder, and the uVNTR and EcoRV polymorphisms of the MAO-A gene, both individually and as a haplotype, were investigated among male adults recruited from jails in Taipei. A total of 129 Chinese Han males were studied, including 41 with antisocial personality disorder with alcoholism, 50 with antisocial personality disorder but without alcoholism, and 38 without either disorder as a jail control group. The diagnoses of alcohol dependence and antisocial personality disorder were made according to DSM-IV criteria. In addition, 77 normal controls were collected from the community. RESULTS: Strong linkage disequilibrium was found for the uVNTR and EcoRV variants of MAO-A gene in each study group. CONCLUSIONS: No significant association was observed between these two polymorphisms and antisocial personality disorder with alcoholism, either individually or for the haplotype, or for antisocial personality disorder without alcoholism. Thus, neither antisocial alcoholism nor antisocial personality disorder was associated with the genetic variants of MAO-A gene.

Alcoholism↗