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)

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

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

Enzymes encoded by two gene families, alcohol dehydrogenase ( ADH) and aldehyde dehydrogenase ( ALDH), mediate alcohol metabolism in humans. Allelic variants have been identified that alter metabolic rates and influence risk for alcoholism. Specifically, ADH1B*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption. In the current study, variants at ADH1B (previously ADH2), ADH1C (previously ADH3), and ALDH2 were assayed in DNA extracts from participants belonging to a Southwest American Indian tribe ( n=490) with a high prevalence of alcoholism. Each subject underwent a clinical interview for diagnosis of alcohol dependence, as well as evaluation of intermediate phenotypes such as binge drinking and flushing response to alcohol consumption. Detailed haplotypes were constructed and tested against alcohol dependence and related intermediate phenotypes using both association and linkage analysis. ADH and ALDH variants were also assayed in three Asian and one African population (no clinical data) in order to provide an evolutionary context for the haplotype data. Both linkage and association analysis identified several ADH1C alleles and a neighboring microsatellite marker that affected risk of alcohol dependence and were also related to binge drinking. These data strengthen the support for ADH as a candidate locus for alcohol dependence and suggest further productive study.
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PMID:Allelic variation at alcohol metabolism genes ( ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. 1288

This article summarizes a symposium that was organized by Dr. Kim Fromme and presented at the 2003 annual meeting of the Research Society on Alcoholism in Ft. Lauderdale, Florida. The four presentations illustrate the emerging technologies and methods that are now being used to investigate the genetic basis of differential sensitivity to alcohol and their behavioral manifestations. Combining human genotyping with laboratory measures of behavior and subjective reports, these presentations represent state-of-the-art approaches to crossing the bridge from the Decade of the Brain to the Decade of Behavior. Dr. De Wit's paper describes her research on the neurobiological basis for individual differences in sensitivity to the stimulant and sedative effects of alcohol. Evidence suggests that activity of the dopaminergic and GABAergic neurotransmitters underlie these stimulant and sedative effects, respectively. Both Drs. Hutchison's and Corbin's papers describe their research on polymorphisms for the serotonin transporter (SLC6A4) as a determinant of the subjective effects of alcohol challenge. Dr. Hutchinson's and Ms. Ray's findings indicate that individuals with the short form of the SLC6A4 alleles (S) demonstrated a low level of response to alcohol, thus supporting previous research that the S allele may be associated with increased risk for alcohol dependence. In contrast, Dr. Corbin did not find a reliable association between the SLC6A4 genotype and subjective response to alcohol. Mr. Cook's and Dr. Wall's paper adds another dimension to this article by presenting research on both the aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH2) genetic variants and their association with the alcohol-related flushing response that is prevalent in Asian populations. Dr. David Goldman provides concluding remarks.
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PMID:Biological and behavioral markers of alcohol sensitivity. 1511 32

Alcohol abuse is associated with many health problems, especially skin changes. As a small, water- and lipid-soluble molecule, alcohol reaches all tissues of the body and affects most vital functions. Cutaneous diseases are now emerging as useful markers of alcoholism detectable at an early and possibly reversible stage of the disease, thus being of substantial importance to dermatologists and general practitioners. The most common skin manifestations of alcoholism presented in this review article are urticarial reactions, porphyria cutanea tarda, flushing, cutaneous stigmata of cirrhosis, psoriasis, pruritus, seborrheic dermatitis, and rosacea.
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PMID:Skin diseases in alcoholics. 1536 44

Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.
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PMID:Alcoholism: genes and mechanisms. 1558 75

Disulfiram (Antabuse) is used for aversive treatment of alcohol dependence with good effects. Through inhibition of aldehyde dehydrogenase, disulfiram heightens serum aldehyde concentration after alcohol ingestion and causes aversive disulfiram-ethanol reaction. Typical symptoms of this reaction include flushing, nausea, dyspnea, tremor, and confusion, which are usually self-limiting. However, severe life-threatening arterial hypotension sometimes develops. We report here a patient with generalized flushing, tremor, and refractive hypotension after ingestion of alcohol 18 hours after disulfiram treatment. Initial volume resuscitation and dopamine infusion failed to restore the blood pressure. Noradrenaline was given and the blood pressure returned to normal range. This case illustrates the intensity of disulfiram-ethanol reaction and underscores the advantageous use of noradrenaline in patients in such a critical condition.
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PMID:Refractive hypotension in a patient with disulfiram-ethanol reaction. 1722 Jun 94

Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P<2.3 x 10(-4)) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P<0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P=8.2 x 10(-7)), consumed alcohol on more occasions (P=2.7 x 10(-6)), had a higher maximum number of alcoholic drinks in a single day (P=2.7 x 10(-6)) and a higher overall alcohol consumption (P=8.9 x 10(-8)) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P=4.7 x 10(-5)) and suggestive associations (P<0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes.
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PMID:Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis. 1899 23

This review summarizes recent findings from human research regarding genetic influences in alcohol abuse and dependence. Genes explain about 50% of the vulnerabilities leading to heavy drinking and associated problems. Most genetic influences appear to impact at least four prominent intermediate characteristics (phenotypes) that interact with environmental events to produce the alcoholism risk: a flushing response to alcohol; a low level of response to alcohol; personality characteristics that include impulsivity, sensation seeking, and neuronal and behavioral disinhibition; and through psychiatric symptoms. Polymorphisms potentially related to each phenotype have been identified, and studies were conducted to evaluate their characteristics in the context of environmental and psychosocial forces. A search is underway to identify genes that contribute to these phenotypes; the ultimate goals of which are better prediction of how to best prevent heavy drinking and problems, identifying individuals who may respond best to existing treatments, and development of new therapeutic approaches based on the biological underpinnings of alcoholism.
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PMID:An overview of genetic influences in alcoholism. 1906 48


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