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

Abstract

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...

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

“…Thirty-three studies dealt with ADH2, 2 [2][3]6,8,11,[26][27][29][30][31][32]37,[39][40][41][42][43][44]46,47,51 and 20 studies in CYP2E1. 6,11,26,31,32,35,[41][42][43]54,[57][58][59][60][61][62][63][64][65]67 To investigate the association between any of the four loci considered and alcohol-induced liver disease, ten studies dealt with ADH2, 5,6,[31][32][33]35,44,49,50,…”

“…For the ALDH2 polymorphism, all studied individuals but 1 among Mexican Americans 26 in alcoholism and 1 among Caucasians 31 in alcoholic liver disease, were homozygous for the *1/*1 genotype in Caucasians and Americans; therefore, the analysis was restricted to East Asians. [2][3][4]8,11,27,28,32,35,37,[39][40][41][42][43][44]46,56,57 There was heterogeneity among studies (P Ͻ .01), and the allele contrast was highly significant (RE OR ϭ 4.35 [95% CI 3.04, 6.23]). The recessive and dominant models for the effect of allele ALDH2*1 showed highly significant associations.…”

Mechanisms of alcohol‐induced hepatic fibrosis

“…Indeed, the presence of super-active alcohol dehydrogenase (ADH2) and inactive aldehyde dehydrogenase (ALDH2) alleles has been linked to increased risk for ALD in Asian populations. 38,39 Both of these gene products will result in an excess accumulation of acetaldehyde.…”

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

“…Alcohol metabolism is one of the biological determinants that can significantly influence drinking behavior and the development of alcohol dependence (2). Alcohol dehydrogenase (ADH), aldehyde dehydrogenase and microsomal ethanol-oxidizing system (MEOS/CYP2E1) allele and genotypes occur at different frequencies in particular ethnic groups, and their role in the development of alcohol dependence differs between races and populations (3)(4)(5)(6)(7)(8)(9)(10)(11). These enzymes play a role in the variation in health effect outcomes seen in different populations owing to alcohol consumption.…”