Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase-3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p less than 0.05 and p less than 0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p less than 0.001). Aldehyde dehydrogenase activity was not different between cirrhosis-free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p less than 0.01). These results suggest that no phenotypic pattern of alcohol dehydrogenase-3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis.
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PMID:Polymorphism of alcohol dehydrogenase, alcohol and aldehyde dehydrogenase activities: implication in alcoholic cirrhosis in white patients. The French Group for Research on Alcohol and Liver. 832 17

Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three beta subunits) and ADH3 (producing two tau subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol-related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele-specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction. All patients and all but one control subject were homozygous ADH2*1, encoding the beta 1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p less than 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage.
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PMID:Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. 193 84

To clarify the pathogenetic role of acetaldehyde in the development of alcoholic liver disease, genotyping of aldehyde dehydrogenase-2 genes was performed and the clinical features of the alcoholic liver disease patients with different genotypes were compared. Genotyping of aldehyde dehydrogenase-2 was performed in 47 patients with alcoholic liver disease using the polymerase chain reaction and slot-blot hybridization. Of the 47 patients with alcoholic liver disease, 40 were homozygous for the normal aldehyde dehydrogenase-2 gene and the remaining seven cases were heterozygous for the normal and mutant aldehyde dehydrogenase-2 genes. No homozygote was found for the mutant aldehyde dehydrogenase-2 genes. Daily alcohol intake was less than 100 gm in all heterozygotes without relation to the type of alcoholic liver disease. On the other hand, all but four patients homozygotic for the normal aldehyde dehydrogenase-2 gene drank more than 100 gm alcohol/day. The mean daily alcohol intake in the heterozygotes was significantly lower than that in the normal homozygotes. The incidence of alcoholic fibrosis tended to be lower in the heterozygotes than in the normal homozygotes (14.2% vs. 52.5%). On the other hand, the incidence of alcoholic hepatitis and/or cirrhosis tended to be higher in the heterozygotes than in the normal homozygotes. These results indicate that alcoholic liver disease develops even with moderate amounts of alcohol intake in heterozygotes of the aldehyde dehydrogenase-2 genes, in which acetaldehyde metabolism in the liver is impaired and liver damage in the heterozygotes is more severe than that in the normal homozygotes, suggesting that habitual drinkers who are heterozygotes of the aldehyde dehydrogenase-2 genes may be at high risk for alcoholic liver disease.
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PMID:Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenase-2 genes. 205 Mar 24

Hepatic aldehyde dehydrogenase isozyme activity was measured in 51 patients with various types of liver diseases, including 24 patients with alcoholic liver disease, to elucidate the relationship between hepatic aldehyde dehydrogenase activity and liver disease, especially alcoholic liver disease. The levels of low-Km and total aldehyde dehydrogenase activity in the liver decreased both in alcoholic and nonalcoholic liver disease patients, who showed an isoelectric focusing pattern of the usual type. There was no significant difference in the aldehyde dehydrogenase activity between alcoholic and nonalcoholic liver disease. In alcoholic liver disease, the decrease in the activity was significantly correlated with the progression of liver histology. The activity in liver cirrhosis was significantly lower than that in the other types of alcoholic liver disease. In nonalcoholic liver disease patients, the unusual type of hepatic aldehyde dehydrogenase activity observed was not different from the unusual type observed in nonhepatobiliary disease patients. These results indicate that the reduction of hepatic low-Km aldehyde dehydrogenase activity is a change that occurs subsequent to liver damage. Genetic abnormality in aldehyde dehydrogenase may not be important in the pathogenesis of alcoholic liver injury.
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PMID:Hepatic aldehyde dehydrogenase activity in liver diseases, with particular emphasis on alcoholic liver disease. 270 38

The hepatic activities and the isoenzyme patterns of both alcohol dehydrogenase and aldehyde dehydrogenase have been studied in 60 alcoholics with varying degrees of liver damage (from normal tissue or minimal changes to cirrhosis with alcoholic hepatitis) and in 24 nonalcoholics with chronic hepatitis or cirrhosis in order to ascertain their association with liver damage. In alcoholics both alcohol dehydrogenase and low-Km aldehyde dehydrogenase activities decreased proportionally with the severity of liver disease. In contrast, in nonalcoholics, there was a reduction of low-Km aldehyde dehydrogenase activity related to the severity of liver injury, but alcohol dehydrogenase was similar in patients with chronic hepatitis and nonalcoholic cirrhosis. There were no significant changes in total and high-Km aldehyde dehydrogenase activities among the different histologic groups studied, although the lowest activities were observed in patients with more severe liver injury. The prevalence of atypical alcohol dehydrogenase was similar in alcoholic (6.6%) and in nonalcoholic (8.3%) liver disease. All patients exhibited isoenzyme aldehyde dehydrogenase II, whereas isoenzyme I was not detected in 39.5% of the alcoholic patients and in 9.5% of those with nonalcoholic liver disease. The lack of aldehyde dehydrogenase I was observed in cases with the lowest enzymatic activities. These results suggest that the decrease of alcohol and aldehyde dehydrogenase activities in alcoholics is not a primary defect and, therefore, their decrease is secondary to liver damage. It is speculated that the diminution of alcohol dehydrogenase, found particularly in alcoholics, could be due to centrilobular cell necrosis.
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PMID:Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases. 275 31

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes. 292 May 34

In a retrospective review of 2400 consecutive liver biopsy specimens, 60 cases with ground-glass hepatocytes were identified, 41 specimens gave a positive reaction to orcein stain and 19 a negative staining. These 19 specimens were obtained from chronic alcoholics who had been admitted to a detoxication program that used aversive drugs and who were hepatitis B surface antigen negative. The use of cyanamide (Colme), an inhibitor of aldehyde dehydrogenase could be documented in 11 instances. In addition to ground-glass hepatocytes, which were periodic acid-Schiff positive and had a periportal or paraseptal distribution, these liver specimens showed a variety of hepatic lesions: cirrhosis in five cases, portal and periportal inflammation in six, triaditis in five, portal fibrosis in two, and minimal changes in one. Patients with shorter courses of cyanamide were those who had less severe histologic lesions. In three patients who had a liver biopsy carried out before the cyanamide treatment ground-glass hepatocytes were not found. These data indicate that ground-glass hepatocytes that stain with periodic acid-Schiff may develop after cyanamide treatment. They are associated with structural hepatic damage of varied severity in patients submitted to a long-term treatment.
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PMID:Hepatic disease associated with ground-glass inclusions in hepatocytes after cyanamide therapy. 302 Oct 86

A method has been developed for simultaneous analysis of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes in small (2.5 mg) liver biopsy cores by starch gel electrophoresis. All the currently recognized hepatic isoenzymes coded by ADH1, ADH2, ADH3 and ADH4 can be detected as can the five ALDH isoenzymes. Using this technique we have investigated the isoenzyme composition of liver samples from English and Chinese subjects and a group of chronic alcoholics. Pronounced racial differences in frequency of ADH2 and ALDH phenotypes were found--only 2 (4%) of English controls had the "atypical" ADH2 variant whereas this was present in 42 (84%) of Chinese subjects, and whereas all the English subjects had the rapidly migrating mitochondrial isoenzyme of ALDH, this was absent in 27 (54%) of Chinese. No differences in ADH or ALDH phenotype were seen in the chronic alcoholics, all of whom were of English origin, compared with the English controls, but there was a reduction in overall ALDH activity and particularly in the mitochondrial isoenzyme in those with cirrhosis. The reduction in ALDH activity is probably acquired; by limiting acetaldehyde oxidation it could be responsible for the rapid deterioration in liver function in patients who continue drinking excessively.
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PMID:Hepatic ADH and ALDH isoenzymes in different racial groups and in chronic alcoholism. 635 65

The development of hepatocellular carcinoma in rodents treated with different chemical compounds is associated with the appearance in the cytosol of neoplastic liver cells of an unusual aldehyde dehydrogenase isozyme of class 3 (ALDH-3) which is very active with aromatic aldehydes. This tumor-associated isozyme is readily detected by enzyme cytochemistry using the substrate benzaldehyde with NADP as coenzyme. To determine whether human hepatocellular carcinomas express ALDH-3, the activity of this isozyme was examined in frozen sections from 68 echo-guided human liver biopsies. In 54 cases the guided biopsy was performed on one or more nodules suggestive for hepatocellular carcinoma found at ultrasonography within the liver parenchyma. The remaining 14 patients were affected by chronic active hepatitis or cirrhosis. An intense enzymatic activity was ascertained in 5 out of 36 hepatocellular carcinomas. In non-neoplastic liver, in macroregenerative nodules and in metastatic adenocarcinomas enzymatic activity was not detectable. ALDH-3-positive tumors were typical hepatocellular carcinomas (histological grade II and III). These results suggest that ALDH-3 is a phenotype associated with malignancy in human liver tumors.
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PMID:Cytochemical detection of a class 3 aldehyde dehydrogenase in human hepatocellular carcinoma. 779 43

Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH2, ADH3 and ALDH2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH2*2 and ADH3*1 alleles, which encode high maximum velocity beta 2- and gamma 1-ADH subunits, respectively, as well as a lower frequency of the ALDH2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol-related cirrhosis (n = 27), viral hepatitis-related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH2 alleles by using polymerase chain reaction-directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele-specific oligonucleotide probes. We found that the frequencies of the alleles ADH2*2 (57%), ADH3*1 (78%) and ALDH2*2 (9%) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. 790 79


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