Characteristics of Japanese Alcoholics with the Atypical Aldehyde Dehydrogenase 2*2.I. A Comparison of the Genotypes of ALDH2, ADH2, ADH3, and Cytochrome P‐4502E1 Between Alcoholics and Nonalcoholics

Abstract

We examined the genotypes of the aldehyde dehydrogenase (ALDH)-2, alcohol dehydrogenase (ADH)-2, ADH3, and P-4502E1 loci of 53 alcoholics and 97 nonalcoholics. All of the subjects fulfilled the DSM-III-R criteria for alcohol dependence. The control group consisted of 97 subjects who were either hospital staff or students. We also compared the frequencies of homozygous ALDH2*1/1 and heterozygous ALDH2*1/2 genotypes in alcoholics. Our study revealed differences in the allelic frequencies of the ALDH2, ADH2, and ADH3 loci between alcoholics and nonalcoholics. For alcoholics with both homozygous ALDH2*1/1 and heterozygous ALDH2*1/2 genotypes, it was found that ADH2 and ADH3 played important rates. Alcoholics with the heterozygous ALDH2*1/2 genotype showed a significantly higher frequency of ADH2*1/1 than ones with the homozygous ALDH2*1/1 genotype. We assume ADH2*1 plays an important role in the development of alcoholism in alcoholics with the heterozygous ALDH2*1/2 genotype.

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

“…The results of studies of Asian and European populations show that ADH1B*1 predominated among alcohol addicts and suggest a high risk of alcohol addiction (9,(26)(27)(28)(29). Hence, these investigators emphasize the importance of ADH1B*2 protection against developing alcohol dependence (3,24,(30)(31)(32)(33)(34)(35)(36)(37).…”

“…These data suggest that the ADH1C*1 allele and ADH1C*1/*1 genotype are likely to favor alcohol dependence. Different results were obtained in studies of Asian populations (26)(27)(28), which showed that the ADH1C*1 allele has protective effects against excessive alcohol consumption.…”

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

“…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.…”

“…In studies of alcoholism, the distribution of genotypes in the control group departured from HWE in two studies for ADH2, 41,48 in five studies for ADH3, 5,26,29,31,45 in nine studies for ALDH2, 6,8,26,[29][30][31]47,51,56 and in two studies for CYP2E1. 11,60 Because a lack of HWE indicates possible genotyping errors and/or population stratification, a sensitivity analysis was performed excluding studies not in HWE.…”

“…Data from 50 studies that investigated the association between any of the ADH2, ADH3, CYP2E1, and ALDH2 polymorphisms and alcoholism, and alcohol-induced liver disease, met the inclusion criteria and were included in the meta-analysis. 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,…”