Aldehyde dehydrogenase genotypes and male alcohol use disorders: A case‐control study in Khon Kaen, north‐east Thailand

Nanakorn, Somsong; Fukuda, Katsuhiro; Nishiyori, Atsushi; Shibata, Akira; Nakamura, Jun

doi:10.1046/j.1440-1819.1999.00563.x

Cited by 8 publications

(23 citation statements)

References 26 publications

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“…The recessive and dominant models for the effect of allele ALDH2*1 showed highly significant associations. The sensitivity analysis 8,56 did not change the pattern of results. In subgroup analysis for men, the allele contrast and the recessive and dominant models were significant.…”

Section: Adh2mentioning

confidence: 81%

“…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%

“…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.…”

Section: Summary Statisticsmentioning

confidence: 99%

“…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.…”

Section: Adh2mentioning

confidence: 99%

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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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Section: Adh2mentioning

confidence: 81%

Section: Eligible Studiesmentioning

confidence: 99%

Section: Summary Statisticsmentioning

confidence: 99%

Section: Adh2mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2006

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“…In addition to alcohol drinking, environmental, cultural or hereditary background factors such as relative lack of formal education, un-married status, employment involving physical labor, smoking, ADH2 genotype and ALDH2 genotype have been reported as potential risk factors of AUD. [1][2][3][4][5] Ingested ethanol is converted by alcohol dehydrogenase ( ADH ) to acetaldehyde, which is subsequently metabolized, by acetaldehyde dehydrogenase ( ALDH) to acetate. Alcohol dehydrogenase is a zinc metalloenzyme with six classes.…”

Section: Introductionmentioning

confidence: 99%

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese

Nishiyori

Shibata

Ogimoto

et al. 2005

Psychiatry Clin Neurosci

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The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2 , ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.

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Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians

2011

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Alcohol is oxidized to acetaldehyde, which in turn is oxidized to acetate. The aldehyde dehydrogenase 2 gene (ALDH2) is the most important gene responsible for acetaldehyde metabolism. Individuals heterozygous or homozygous for the lys (A or *2) allele at the single nucleotide polymorphism (SNP) glu504lys (rs671) of ALDH2 have greatly reduced ability to metabolize acetaldehyde, which greatly decreases their risk for alcohol dependence (AD). Case-control studies have shown association between this SNP and alcohol dependence as well as alcohol-induced liver disease. However, some studies have produced insignificant results. Using cumulative data from the past 20 years predominately from Asian populations (from both English and Chinese publications), this meta-analysis sought to examine and update whether the aggregate data provide new evidence of statistical significance for the proposed association. Our results (9,678 cases and 7,331 controls from 53 studies) support a strong association of alcohol abuse and dependence, with allelic P value of 3×10−56 and OR of 0.23 (0.2, 0.28) under the random effects model. The dominant model (lys-lys + lys-glu vs. glu-glu) also showed strong association with P value of 1×10−44 and OR of 0.22 (0.18, 0.27). When stricter criteria and various sub-group analyses were applied, the association remained strong (for example, OR = 0.23 (0.18, 0.3) and P = 2×10−28 for the alcoholic patients with alcoholic liver disease, cirrhosis, or pancreatitis). These findings provide confirmation of the involvement of the human ALDH2 gene in the pathogenesis of AD as well as alcohol-induced medical illnesses in East-Asians.

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Aldehyde dehydrogenase genotypes and male alcohol use disorders: A case‐control study in Khon Kaen, north‐east Thailand

Cited by 8 publications

References 26 publications

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

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

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese

Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians

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