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)

Human ethanol consumption has a profound impact on nutritional status, causing major alterations in intermediary metabolism and critical deficiencies of vitamins and trace elements. The major enzyme systems responsible for the principal steps in ethanol metabolism have been characterized and the genes cloned, and significant functional polymorphisms have been identified. An inactive allele of the mitochondrial ALDH is associated with flushing and reduced alcohol intake. This allele may also confer greater sensitivity to some of ethanol's toxic effects. In populations not possessing this variant, twin and adoptive studies have revealed that heritability for alcoholism is greater than 50%. The occurrence of three functional polymorphisms in the ethanol metabolic pathway, including two mutations which are conserved across populations, suggests a role for selection in their maintenance. The two general categories of selective forces to maintain these polymorphisms are food toxins and infectious diseases. Of the infectious agents, amoebi and other anaerobic and microaerophilic organisms of the gut are the most logical candidates.
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PMID:Genetic epidemiology of ethanol metabolic enzymes: a role for selection. 219 94

Inherited deficiency of acetaldehyde dehydrogenase type I (ALDH-I) was found in 43% (50/117) of normals, 33% (27/82) of schizophrenics, but only 4% (5/113) of alcoholics among Japanese. The ALDH-I deficiency was never found, however, in 146 mostly schizophrenic subjects from Europe (Basel, Moscow, Zagreb), Australia (Nedlands), India (Lucknow), Morocco (Casablanca) and Mexico (Mexico City). It was demonstrated that ALDH-I deficiency produces the flushing syndrome which inhibits the development of drinking habit and alcohol dependence syndrome.
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PMID:Biological study of alcohol dependence syndrome with reference to ethnic difference: report of a WHO Collaborative Study. 236 95

Deficiency of mitochondrial aldehyde dehydrogenase (ALDH I) is an inborn error of metabolism that is responsible for acute alcohol sensitivity (flushing response) observed only in Orientals of Mongoloid origin. Our previous studies using electrophoretic enzyme detection have shown that this deficiency is prevalent among Japanese, Chinese, and other Orientals. We report here the genotyping of ALDH I locus in blood samples of 218 South Korean individuals by means of hybridization analysis with allele-specific oligonucleotide probes and enzymatically amplified human genomic DNA. The results of genotyping are compared with the phenotype analysis in hair roots of the same individuals. Among 62 apparently deficient phenotypes, 58 heterozygote and 4 homozygote deficient genotypes were observed.
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PMID:Genotyping of mitochondrial aldehyde dehydrogenase in blood samples using allele-specific oligonucleotides: comparison with phenotyping in hair roots. 270 32

Individual differences in response to alcohol have been observed in various ethnic and racial groups. A positive correlation between alcohol sensitivity and elevated blood acetaldehyde level in conjunction with deficiency of an isozyme of aldehyde dehydrogenase (ALDH I) was noted in Japanese subjects given an acute dose of alcohol. Invariably, significantly higher blood acetaldehyde levels were measured in ALDH I-deficient subjects after ethanol loading. The initial flushing in Orientals after alcohol ingestion might be due to their inability to metabolize acetaldehyde quickly and effectively in the absence of the low Km ALDH I isozyme. While Oriental populations of Mongoloid origin showed varying degree of isozyme deficiency, none of the Caucasian or Negroid populations have this isozyme abnormality.
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PMID:Aldehyde dehydrogenase polymorphism: molecular basis and phenotypic relationship to alcohol sensitivity. 342 17

The metabolism of acetaldehyde has received considerable attention in the past owing to its acute and chronic toxic effects in humans. Two major hepatic ALDH isozymes, ALDH I and ALDH II, differing in their structural and functional properties, have been characterized in humans. ALDH I has a low Km for acetaldehyde and is primarily a mitochondrial enzyme, while ALDH II has a higher Km and is of cytosolic origin. An inherited deficiency of ALDH I isozyme found only among Oriental populations is primarily responsible for producing acute alcohol sensitivity symptoms (flushing response) after consumption of small doses of alcohol. Biochemical, immunochemical, and molecular genetics data indicate a structural mutation in the ALDH I isozyme gene responsible for the loss in catalytic activity. Population genetic studies have revealed the prevalence of ALDH polymorphism among individuals of the Mongoloid race. Flushing response to alcohol is a familial trait, and preliminary family data from Japan, China, and Korea suggest an autosomal codominant inheritance for ALDH I isozyme deficiency. The ALDH polymorphism is apparently responsible for the low incidence of alcoholism in Japanese, Chinese, and Koreans. Alcohol sensitivity due to ALDH I isozyme deficiency may inhibit excessive alcohol drinking.
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PMID:Human aldehyde dehydrogenase isozymes and alcohol sensitivity. 361 May 92

Normal Japanese subjects were divided into two groups, i.e., one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde, and the other deficient in the low Km isozyme. After intake of 0.4 g/kg alcohol, the deficient subjects showed high level of blood acetaldehyde, facial flushing and the other dysphoric symptoms, including increase of pulse rate, decrease of diastolic blood pressure, changes of pulse wave in the fingertip, and elevation of the arterial pressure and blood flow rate in common carotid arteries as well as increase of plasma catecholamines level. In contrast, subjects with normal ALDH did not show these changes. From the observation of liver specimens obtained at autopsy, the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%.
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PMID:Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese. 635 56

While most Caucasians have two main isozymes of liver aldehyde dehydrogenase, in about 50% of Orientals the ALDH I isozyme is missing. This isozyme, which has a faster electrophoretic mobility, is predominantly present in mitochondria and has a relatively low Km for acetaldehyde. The inherent deficiency of ALDH I is responsible for the impaired acetaldehyde oxidation leading to facial flushing and other cardiovascular symptoms of alcohol sensitivity commonly observed in Japanese and Chinese. Antibodies raised against apparently homogeneous liver ALDH I and ALDH II isozymes did not show an immunological similarity between the two isozymes which do not share common subunits. While erythrocyte ALDH II is also immunologically distinct from hepatic ALDH I, it showed an immunological similarity with hepatic ALDH II. On isoelectric focusing in agarose gel followed by immunoelectrophoresis, at least 4 components with an anti-ALDH I antibody were detected in extracts from Caucasian and Oriental livers. In Japanese livers deficient in ALDH I activity, the prominent ALDH component was missing. Apparently, more than one gene is responsible for the synthesis of ALDH isozymes reacting with an antibody against ALDH I. A deletion in one of the genes may be responsible for the loss of ALDH I enzyme activity and altered antigenic properties. However, at this stage, a point mutation in a structural gene coding for ALDH I resulting in a defective protein with altered electrophoretic and enzymatic properties is not ruled out.
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PMID:Basis of aldehyde dehydrogenase deficiency in Orientals: immunochemical studies. 653 15

The aldehyde dehydrogenase I (ALDH I) gene codes for a mitochondrial enzyme which plays a major role in hepatic alcohol detoxication. It has been related to alcohol flushing in Orientals bearing the atypical ALDH I2 gene. The variant protein results from a lysine for glutamate substitution at position 487 (G-->A change in exon 12). A procedure for ALDH I2 detection consisting in a differentiation between the 'atypical' allele and the 'wild' allele has been improved through PCR and subsequent MboII digestion. Blood samples collected on anticoagulant or directly absorbed on blotting paper were used for DNA amplification in the presence of two specific oligonucleotidic primers, each one able to incorporate a restriction site in the amplimer. After MboII digestion, PCR products were separated by polyacrylamide gel electrophoresis and then visualized with ethidium bromide. This technique permits a rapid and non-radioactive detection of atypical ALDH I2 on a PCR product without the use of allele specific oligonucleotides. It was applied to the study of ALDH I2 allele frequency in random population samples of three ethnic groups: Caucasians, Orientals and African blacks.
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PMID:The frequency of the mitochondrial aldehyde dehydrogenase I2 (atypical) allele in Caucasian, Oriental and African black populations determined by the restriction profile of PCR-amplified DNA. 747 12

This study investigated the association between the flushing response and alcohol use among Japanese Americans in the greater Los Angeles area. Epidemiolocial data collected through a telephone survey and a mail survey were utilized to test the flushing-alcohol use relationship in the Japanese population, and to explore the effects of socioenvironmental variables. Results showed that, as predicted, those Japanese Americans who exhibited the fast flushing response tended to drink less than those who did not flush, in the general community sample, but the relationship was weaker in the college student sample. Logistic regression analysis identified several covariates that predicted alcohol use among the general community residents: being a male, being single and being of the third/fourth generation. A separate logistic regression analysis with the college students only revealed a moderately significant interaction effect of flushing response and "Greek" affiliation (membership in a campus fraternity or sorority) on alcohol use (i.e., 6 drinks or more in a 24-hour period), indicating that the social context appeared to have a moderating effect on the relationship between the flushing response and alcohol use among Japanese Americans. Eighty out of 300 individuals completely abstained from alcohol consumption and therefore did not know if they possessed the fast-flushing response. Results were discussed with respect to further investigation of the role played by ALDH-I deficiency in varying social situations in the Japanese population.
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PMID:The association between fast-flushing response and alcohol use among Japanese Americans. 835 99

Three methods were employed to assess whether human volunteers (Caucasian, Asian or Cree Indian) possessed the typical or atypical mitochondrial aldehyde dehydrogenase (ALDH2) isozyme. These methods were: (1) questioning individuals about facial flushing responses following alcohol consumption; (2) application of the ethanol skin patch test, and (3) direct analysis using isoelectric focusing and activity staining of ALDH activity in hair root samples. The results from the three methods were in good agreement and revealed that only the typical ALDH2 isozyme was expressed in Saskatchewan Cree Indians. In agreement with previous reports, the typical ALDH2 was expressed in the Caucasian group of subjects, while both the typical and atypical forms were expressed in the Asian subjects.
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PMID:Absence of the atypical mitochondrial aldehyde dehydrogenase (ALDH2) isozyme in Saskatchewan Cree Indians. 835 13


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