Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined the genotypes of the alcohol dehydrogenase (ALDH) and aldehyde dehydrogenase (ALDH2) loci of different ethnic groups living in Brazil, using saliva DNA amplified by PCR and allele-specific oligonucleotides. Self-reports of flushing reaction after drinking were also studied. The allelic frequencies of ADH2 and ALDH2 were found to be lower than those reported other authors, which might be a result of the admixture origin of the Brazilian population. Variability in facial flushing reaction suggests that other factors play a role in the expression of alcohol-induced flushing.
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PMID:Allele frequency of ADH2 and ALDH2 among Brazilians of different ethnic groups. 916 Jul 96

Mitochondrial aldehyde dehydrogenase (ALDH2) shows genetic polymorphism (Glu487Lys substitution) among Mongoloid populations, and the substitution is responsible for flushing symptom after alcohol intake. Recently, new ALDH2 alleles (ALDH2*3 and ALDH2*2Taiwan) in exon12 were reported in North American Indians and in Chinese from Taiwan by Novoradskey et al (1995). In the present study, we investigated the new allelic variants in exon12 for the five different ethnic groups (Mongolian, North Chinese, South Chinese, Myanmar, Japanese) by using PCR-SSCP and PCR-direct sequencing. Also, Glu 487 Lys substitution was analyzed to obtain additional information on gene geography of ALDH2 alleles in Asia reported so far. No new variants were found in the five population groups, but ALDH2*2 allele showed different frequencies among these groups. Especially, the frequencies of ALDH2*2 in Myanmer (0.02) and Mongolian (0.05) were significantly lower than other populations.
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PMID:[Investigation for polymorphism of ALDH2 exon12 in several Asian areas]. 961 2

The aims of this study are to investigate whether self-reported facial flushing postalcohol consumption (PAC) among subjects with ALDH2*1/*1 can be attributed to ADH2 or ADH3 and whether the prediction of ALDH2 genotype can be improved by examining the combination of flushing and other accompanying reactions of PAC sensitivity. Fifty-eight subjects of Han ancestry in Taiwan were interviewed for alcohol-sensitivity reactions and their blood samples were genotyped for ALDH2, ADH2, and ADH3. For subjects with ALDH2*1/*1 (n = 46), 70% reported to have no flushing PAC and 30% reported flushing PAC. When subjects with ALDH2*1/*1 had ADH2*1/*1 (n = 11), all reported to have no flushing; otherwise, 35% (for ADH2*1/*2, n = 17) and 44% (for ADH2*2/*2, n = 18) reported flushing. For subjects with ALDH2*1/*1 and at least one ADH2*2 allele, the genotype of ADH3 was not associated with self-reported flushing. PAC flushers with ALDH2*1/*1 (50%) were more likely to report nausea than those with ALDH2*1/*2 (8%). The probability of ALDH2*1/*1 given flushing reported was 0.29, while the probability of ALDH2*1/*1 given both flushing and nausea reported was 0.71. The results indicate that self-reported flushing is determined by both ALDH2 and ADH2 and that prediction of ALDH2 genotype on the basis of self-reported flushing and nausea can help identify subjects at increased risk for alcoholism.
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PMID:Self-reported flushing and genotypes of ALDH2, ADH2, and ADH3 among Taiwanese Han. 972 71

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.
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PMID:Development of a questionnaire method to discriminate between typical and atypical genotypes of low Km aldehyde dehydrogenase in a Japanese population. 980 21

High alcohol sensitivity common among Orientals is mainly due to genetic polymorphism in the low K(m) aldehyde dehydrogenase (ALDH2) gene. The relation of the ALDH2 genotype to alcohol sensitivity and drinking behavior was investigated in a Japanese occupational population. The frequency of alcohol-associated symptoms generally increased in the order of the typical homozygote, heterozygote, and atypical homozygote. Both drinking frequency and amounts of alcohol consumption were also significantly affected by the polymorphism. Polymorphism in the alcohol dehydrogenase beta-subunit (ADH2 gene) appeared to contribute to skin flushing post-alcohol exposure but not to alcohol drinking behavior. Multivariate analysis revealed that high alcohol consumption, the ALDH2*1/*1 genotype, and high daily hassles levels significantly contribute to the prevalence of those with a high problem-drinking score in an occupational population. In the study to assess the effects of the ALDH2 polymorphism and alcohol use on the induction of chromosome alterations in peripheral lymphocytes, we found that lymphocytes from habitual drinkers with the atypical ALDH2 genotypes had significantly higher frequencies of sister-chromatid exchange (SCE) than those from the typical ALDH2 genotype. We also measured acetaldehyde reversibly bound to hemoglobin (HbAA). In volunteers with the ALDH2*1/*2 genotype, the HbAA levels increased immediately after the drink and the elevated levels persisted up to 48 h. Among male workers, HbAA levels were significantly correlated with the recent alcohol consumption levels in both the ALDH2*1/*1 and ALDH2*1/*2 genotypes. However, the slope was much steeper in the ALDH2*1/*2 than in the ALDH2*1/*1. SCE and HbAA may be utilized as a good biomarker for health problems in the atypical ALDH2 genotype. Further extensive studies are required for evaluation of the interactive effects of genetic and environmental factors on alcohol-related health problems.
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PMID:[Genetic factors which regulate alcohol drinking behavior and their effects on health status]. 1047 85

Multiple forms and gene loci of human alcohol dehydrogenase (ADH EC: 1.2.1.3) and aldehyde dehydrogenase (ALDH, EC: 1.2.1.3) in the major pathway of alcohol metabolism have been found and characterized in the last two decades. With the coenzyme NAD, these enzymes catalyze the reversible conversion of organic alcohols to ketones or aldehydes, and aldehyde to acetic acid. The ADH genes are mapped to chromosome 4p21-25, but the ALDH genes are localized at different chromosomes. The cytochrome P450 2E1 (CYP2E1) gene, which is mapped to chromosome 10q24.3-qter contributes also the conversion of ethanol to acetaldehyde. Genetic polymorphisms have been reported in these alcohol metabolizing enzymes. The metabolisms of alcohol and acetaldehyde in liver and blood after drinking alcohol are thought to be influenced by the interactive action of these enzymes. Amongst the five major classes of the ADH subunits (alpha, beta, gamma, pi, chi, sigma), beta and gamma subunits show genetic polymorphisms. Recently a new nomenclature for ALDH genes has been recommend based on divergent evolution and chromosomal mapping. Two major isoforms designated as cytosolic ALDH1 and mitochondrial ALDH2 can be distinguished by their electrophoretic and kinetic properties as well as by their subcellular localization. Mitochondrial ALDH2 is a major enzyme in the oxidation of acetaldehyde derived from ethanol metabolism. The catalytic deficiency of ALDH2 isozyme is responsible for flushing and other vasomotor symptoms caused by higher acetaldehyde levels after alcohol intake. So far, frequencies of the two alleles of ALDH2 in Mongoloid have been reported in the different population groups. The catalytic deficiency of ALDH2 is caused by a structural point mutation at amino acid position 487, where a substitution of Glu to Lys resulting from a transition of G (C) to A (T) at 1510 nucleotide from the initiation codon has occurred. Individuals deficient in ALDH2 activity refrain from excessive drinking of alcohol due to the aversive reactions, leading to protection against alcoholism. Prevalence of the ALDH2*1 allele is associated with alcoholism, and subsequent studies have confirmed the allelic association with alcoholism in different ethnic groups. The effects of polymorphisms of ADH2 and CYP2E1 remained controversial, even in the same ethnic group. Investigation of mutations for the transacting cis-element in promoter region of the ALDH2 gene will provide important information with respect to regulation of this gene. Transfection assays using the first 600 bp of the upstream nucleotide sequences indicated that a region from -75 to -120 was necessary for the ALDH2 gene expression, and especially NF-Y/CP1 binding site from -92 to -96 (CCAAT box) is important in the expression of the gene. A novel polymorphism due to the nucleotide replacement at -357 G to A was found in all the population groups. Alcoholism is thought to be a multifactorial disease with complex mode of inheritance in addition to psychological and social factors, and many studies of family, adoption and twins concerning alcoholism have revealed that hereditary factor is an important determinant for developing alcoholism. Genetic association studies have contributed to the identification of a number of genetic risk factors for the chronic diseases influenced by genetic disorders and environmental factors.
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PMID:[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese]. 1139 42

A variety of genetically influenced alcohol-related phenotypes relate to risk for alcohol dependence. In Asians, variation in the alcohol dehydrogenase (ADH2) gene relates to alcohol dependence, alcohol consumption, and reported alcohol-related symptoms, even after controlling for variation in the aldehyde dehydrogenase (ALDH2) gene. The association of ADH2 polymorphisms with alcohol-related behavior, however, has not been well characterized in non-Asians. This study evaluated 84 Ashkenazic Jewish American college students to determine the prevalence of the ADH2*2 allele (0.31). Carriers of ADH2*2 reported significantly fewer drinking days per month. ADH2*2, however, was not related to alcohol use disorders, alcohol-induced flushing and associated symptoms, number of binge drinking episodes in the past 90 days, maximum number of drinks ever consumed, or self-reported levels of response to alcohol. Results suggest that Ashkenazic Jewish Americans with ADH2*2 alleles drink less frequently, which might contribute, in part, to the overall lower rates of alcoholism in this population.
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PMID:ADH2 and alcohol-related phenotypes in Ashkenazic Jewish American college students. 1154 39

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.
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PMID:Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers. 1267 87

The drinking behavior, alcohol-induced facial flushing and ALDH2 genotypes were determined in 283 Thai men comprising 85 who were alcohol-dependent, 62 hazardous/harmful drinkers and 136 non-drinkers or infrequent drinkers. A structured interview questionnaire, containing the 'tri-level' method and the Alcohol-Use Disorders and Associated Disabilities Schedule, was used to determine the quantity of drinking and the number of alcohol-related adverse experiences. The study revealed the mutant ALDH2*2 allele in 44 (15.5%) subjects. The risks of being alcohol-dependent and of having hazardous/harmful drinking were lower in individuals with heterozygous ALDH2*1/*2, compared with homozygous ALDH2*1/*1 [relative probability ratios (95% CI) 0.14 (0.05-0.41) and 0.23 (0.08-0.61), respectively]. Eighty percent of those who were heterozygous and 28% of those who were homozygous ALDH2*1 reported flush symptoms after drinking alcohol. Twenty-nine percent of homozygous ALDH2*1 individuals, but only 9% of heterozygous subjects, drank almost everyday (24-30 days/month). Similarly, higher percentages of people drinking beyond the safety limit (>60 g/day) and having alcohol-related problems were observed in homozygous ALDH2*1 compared with heterozygous individuals: 32% vs. 5% and 27% vs. 12%, respectively. Overall, the study supports the role of the mutant ALDH2*2 allele in preventing high alcohol consumption and the development of alcohol dependence in a Thai population.
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PMID:Aldehyde dehydrogenase 2 genotypes, alcohol flushing symptoms and drinking patterns in Thai men. 1275 56

High alcohol sensitivity among Asians is mainly due to a genetic polymorphism in the low Km aldehyde dehydrogenase (ALDH2) gene. Strong correlations between the ALDH2 genotype and alcohol sensitivity or alcohol drinking habits have been reported. Another prevalent polymorphism in the alcohol dehydrogenase beta-subunit (ADH2 gene) among Asians appears to modify skin flushing reactions after exposure to ethanol but does not influence alcohol drinking behavior. Both the ADH2 and ALDH2 genotypes have been significantly correlated with the risk of alcoholism. In a Japanese occupational population, a gene-environment interaction of the ALDH2 genotype and daily hassles scores for development of problem drinking behavior was observed. Habitual drinkers with the ALDH2*1/*2 genotype had higher frequencies of sister-chromatid exchange in cultured lymphocytes and higher 8-OHdG levels in polymorphonuclear leukocytes than those with the ALDH2*1/*1 genotype. Alcoholics and heavy drinkers with the ALDH2*1/*2 genotype have been shown to have significantly elevated risks for esophageal and multiple cancers in upper digestive organs than those with the ALDH2*1/*1 genotype. In Japan, bronchial asthma patients with the ALDH2*1/*2 genotype have been shown to have a significantly elevated risk for experiencing alcohol-induced asthma compared with the ALDH2*1/*1 genotype. Providing services to determine these genotypes would be of great help for each individual to make a plan for tailor-made health promotion.
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PMID:[Gene-environmental interactions in alcohol-related health problems--contributions of molecular biology to behavior modifications]. 1280 63


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