Alcohol dehydrogenase ADH2–1 and ADH2–2 allelic isoforms in the Russian population correlate with type of alcoholic disease

Ogurtsov, Pavel; Гармаш, И. В.; Мяндина, Г. И.; Guschin, Alexander; Itkes, A.V.; Моисеев, В С

doi:10.1080/13556210020077109

Cited by 32 publications

(29 citation statements)

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“…The hazard ratio of hospitalization for alcoholism in men and women with the slow alcohol degradation ADH1B Á 1/1 genotype was 3.9 (95% CI: 1.0-16) and 2.7 (95% CI: 0. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Section: Resultsmentioning

confidence: 99%

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

et al. 2007

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Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B Á 1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B Á 1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B Á 1/1 genotype compared to men with the ADH1B Á 1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C Á 1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B Á 2/2 genotype, compared with men with the ADH1C Á 1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B Á 1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

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Section: Resultsmentioning

confidence: 99%

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

et al. 2007

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“…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,…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Eight studies in alcoholism 28,33,38,39,44,56,65,66 and two studies in liver disease 33,44 reported that the controls were age-or sex-matched. Studies were conducted in various populations of racial background: 24 involved Caucasians, 5 …”

Section: Eligible Studiesmentioning

confidence: 99%

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

et al. 2006

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Case-control studies that have investigated the association between alcoholism and alcoholinduced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2* . When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results. O ver the last few years, an increasing number of studies have provided compelling evidence for the involvement of genetically defined predisposing factors in alcoholism and alcohol-induced cirrhosis. The strongest support comes from the fact that not all subjects with a high daily intake of alcohol develop alcohol-induced liver disease. Mostly metabolized in the liver by the successive action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the rate of conversion of ingested ethanol to acetaldehyde, and of acetaldehyde to acetate, is influenced by genetic polymorphisms at both loci. ALDH2 is the most important gene that affects predisposition to alcoholism in Asian populations. Thus, the prevalence in these populations of the inactive ALDH enzymatic form encoded by the ALDH2*2 allele appears to protect against alcoholism. 1 Furthermore, alcoholics with this inactive allele may be at great risk for advanced alcoholic liver disease. [2][3][4] Regarding the ADH gene cluster, polymorphisms are also detected at the ADH2 and ADH3 loci with two alleles (referred to as *1 and *2) each. Alleles ADH2*2 and ADH3*1 encode, respectively, for the highly active ␤ 2 and ␥ 1 allozymes, 5 and a low prevalence of both alleles has been reported in alcoholic Asians-although some studies did not detect associations between ADH3 polymor-

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“…The ADH1B 48His allele is relatively rare in Caucasians with a frequency of 0-10% [6,[11][12][13][14][15] except in Russia where one study found it in 41% [16]. This allele is more frequent among Asian populations, where its frequency varies from 50 to 90 percent, depending on ethnicity [15,17].…”

Section: Introductionmentioning

confidence: 99%

Combined Effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 Alleles on Alcoholism and Chronic Liver Diseases

et al. 2011

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Abstract. The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary. The study included men, aged 45-64 years. Altogether, 241 cases with chronic liver disease (CLD) and 666 randomly selected controls without CLD were analysed for all four polymorphisms. Associations between the polymorphisms, individually, and in combination, and excessive and problem drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage. The 272Gln/350Val allele increased the risk of excessive and problem drinking in homozygous form (OR = 1.582, p = 0.035, CI = 1.034-2.421, OR = 1.780, p = 0.016, CI = 1.113-2.848, respectively). The joint analysis showed that when combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is protective against CLD (OR = 0.368, p = 0.019, CI = 0.159-0.851). The results obtained in the study help not only to clarify the effects of different ADH SNPs but to better understand how these polymorphisms modify each other's effects in the development of alcoholism and related diseases.

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Alcohol dehydrogenase ADH2–1 and ADH2–2 allelic isoforms in the Russian population correlate with type of alcoholic disease

Cited by 32 publications

References 10 publications

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

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

Combined Effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 Alleles on Alcoholism and Chronic Liver Diseases

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