Genetics of Human Alcohol-Metabolizing Enzymes

Yoshida, Akira; Hsu, Lily C.; Yasunami, Michio

doi:10.1016/s0079-6603(08)60844-2

Cited by 187 publications

(104 citation statements)

References 104 publications

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“…Most of the acetaldehyde generated during alcohol metabolism in vivo is promptly eliminated by ALDH2, a low-Km mitochondrial ALDH [3] . The gene for the homotetrameric enzyme ALDH2 has a polymorphism and its mutant ALDH2 *2 allele (Glu487Lys, Lys or A allele) encodes a catalytically inactive subunit [4] . ADH2 is also polymorphic and its mutant ADH2*2 allele (Arg47His) encodes a superactive subunit of ADH2 [3,4] .…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

Gao¹,

Takezaki²,

Wu³

et al. 2008

WJG

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AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2 ) and/or aldehyde dehydrogenase 2 (ALDH2 ) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-control study was conducted in 190 cases and 223 population-based controls. ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A) genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC). Information on smoking and drinking was collected and odds ratio (OR) was estimated. RESULTS:

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Section: Introductionmentioning

confidence: 99%

Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

Gao¹,

Takezaki²,

Wu³

et al. 2008

WJG

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“…The most reliable alcohol drinkexchange at position 487 of the subunit protein. 7 After amplification and digesing history was the average monthly intake, checked by the patient's tion with MboII, ALDH2*1 alleles give rise to 55-bp, 26-bp, and 10-bp PCR spouse, and acquired after a good doctor-patient relationship had products and ALDH2*2, 65-bp and 26-bp products. Undigested PCR products, been well established.…”

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confidence: 99%

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients

et al. 1997

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The physical complications of alcoholism are numerous. It is still not clear why some alcoholic patients acquireDifferent mechanisms are probably involved in different alcocertain organ-specific complications of alcoholism hol-induced end organ diseases, such as those in the liver, whereas other alcoholic patients acquire different ones.pancreas, heart and neuromuscular system. It is still not As we know the liver alcohol dehydrogenase (ADH), clear why some alcoholic patients acquire certain organ-spealdehyde dehydrogenase (ALDH), and cytochrome cific complications of alcoholism, whereas other alcoholics ac-P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, quire different ones. and ALDH2 loci and the 5-flanking region of the Alcohol is metabolized in the hepatocyte via three path-P4502E1. The aim of this study was to investigate the ways: the alcohol dehydrogenase (ADH) pathway in the cytodifferences between Chinese alcoholic patients with cirsol, the microsomal ethanol oxidizing system in the endoplasrhosis and acute pancreatitis by studying the genetic mic reticulum, and catalase in the peroxisomes. ADH and polymorphisms of ADH2, ADH3, ALDH2, and P4502E1.the microsomal ethanol oxidizing system produce specific Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was metabolic and toxic disturbances, and all three pathways reperformed using polymerase chain reaction-restriction sult in the production of acetaldehyde, which then is metabofragment length polymorphism (PCR-RFLP) methods on lized by aldehyde dehydrogenase (ALDH) into acetate.2-4 Acperipheral white blood cell DNA from 75 alcoholic cir-etaldehyde, a metabolite more toxic than alcohol itself, is one rhotic patients, 48 acute alcoholic pancreatitis patients, of several factors implicated in the onset or development of 19 heavy drinkers without liver disease or pancreatitis, cirrhosis.5 Genetic polymorphisms in ADH2, ADH3, and and 235 controls. The results showed that the frequen-ALDH2 and in the 5-flanking region of the human cytocies of the alleles ADH2*1 and ALDH2*1 in the alcoholic chrome P4502E1 gene (P4502E1) and its ethnic variations cirrhotic patients were significantly higher than those have been reported.2-14 A number of studies have looked for in the nonalcoholic controls. In acute alcoholic pancre-differences in alcohol metabolizing enzymes to explain susatitis patients, only the frequency of allele ALDH2*1, not ceptibility to alcoholism and to alcohol-induced liver dis-ADH2*1 was significantly higher than in the nonalco-ease. [3][4][5][9][10][11][12][15][16][17][18] We previously reported that the ADH2*1, holic controls. The allele frequency of ADH2*1 in acute ADH3*2, and ALDH2*1 genes can affect predisposition to pancreatitis patients was significantly lower (P õ .01) alcoholism in Chinese patients. 15 In that study, we investithan in alcoholic cirrhotic patients. The daily amount of gated only alcohol-induced cirrhotic patients but no other alcohol consumption was significantly lower in patients subpopulation of alcoholic patients with differ...

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“…ALDH2 has the highest affinity for acetaldehyde, an important intermediary product of ethanol metabolism. Although acetaldehyde is also detoxified by other ALDH isozymes, including cytosolic ALDH1A1 and mitochondrial ALDH1B1, ALDH2 is the primary ALDH responsible for the clearance of ethanol-derived acetaldehyde [3,18,25].…”

Section: Aldh2mentioning

confidence: 99%

Roles of defective ALDH2 polymorphism on liver protection and cancer development

Matsumoto

Thompson

Chen³

et al. 2016

Environ Health Prev Med

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Genetics of Human Alcohol-Metabolizing Enzymes

Cited by 187 publications

References 104 publications

Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients

Roles of defective ALDH2 polymorphism on liver protection and cancer development

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