Alcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines

Chen, Wei-Jen; Loh, E. W.; Hsu, Yun-Pung P.; Cheng, Andrew Tai Ann

doi:10.1016/s0006-3223(96)00072-8

Cited by 76 publications

(78 citation statements)

References 26 publications

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“…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,…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Although the majority of studies reviewed in this meta-analysis reported on more than two of the investigated polymorphisms, only four of them provided analyses of haplotypes. 7,8,37,40 Seven studies [5][6][7][8]31,37,40 investigated the existence of linkage disequilibrium, and six demonstrated linkage disequilibrium between ADH2 and ADH3. 5,7,8,31,37,40 Because all studies provided unadjusted estimates, adjusted pooled OR were not calculated.…”

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: Eligible Studiesmentioning

confidence: 99%

Section: Summary Statisticsmentioning

confidence: 99%

Section: Adh2mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2006

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“…Studies on the genotype and phenotype of ALDH2 showed that the genotype of ALDH2 was related to the occurrence and development of excess alcohol consumption and alcohol-related diseases (Morimoto and Takeshita, 1996;Chen et al, 1997Chen et al, , 1999, and null ALDH2 activity was found in about 50% of the Mongolian population (Minami et al, 2002). The Mongolian population lives on the Mongolian plateau in North China with cold climate.…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde dehydrogenase 2 SNP rs671 and susceptibility to essential hypertension in Mongolians: a case control study

T¹,

Liang²,

Yang³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Mongolians are known as heavy drinkers, and they have a high incidence of essential hypertension, which may be an associated pathology. We examined a possible association of essential hypertension and polymorphism of the aldehyde dehydrogenase 2 (ALDH2) gene in Mongolians from Inner Mongolia. Single nucleotide polymorphism rs671 of ALDH2 was detected by TaqMan PCR in 91 essential hypertensive patients (44 males and 47 females) and 70 healthy Mongolians (37 males and 33 females). Frequencies of the ALDH2*1/1 genotype and the ALDH2*1 allele in patients (91.2 and 95.6%, respectively) were significantly higher than in controls (78.6 and 89.3%; P < 0.05), while frequencies of ALDH2*1/2 genotype and ALDH2*2 allele in patients (8.79 and 4.4%) were much lower than in controls (21.4 and 10.7%; P < 0.05). Frequencies of ALDH2*1/1 genotype and ALDH2*1 allele in female patients (95.8 and 94.9%) were higher than in female controls (70.0 and 84.9%; P < 0.05); frequencies of the ALDH2*1/2 genotype and the ALDH2*2 allele in female patients (4.25 and 2.13%) were lower than in female controls (30.3 and 15.2%, P < 0.05). There was no significant difference in male subjects. ALDH2*2/2 was not found in any of the subjects. We conclude that ALDH2 polymorphism is associated with essential hypertension in Mongolians, especially in female Mongolians. ALDH2*2 was found to be a negative risk factor for essential hypertension in Mongolians from Inner Mongolia.

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“…This variation is due in part to single nucleotide polymorphisms (SNPs) within the genes that encode the alcohol dehydrogenase (ADH) enzymes (Thomasson et al 1993). One commonly studied exonic SNP allele in ADH1B (variously referred to as Arg47His, ADH1B*2, or ADH2*2, but now called ADH1B*47His) has been associated with protection against alcohol dependence in numerous studies (Chambers et al 2002a;Chen et al 1997;Osier et al 2002), and is common in Asian and Pacific populations (Chambers et al 2002a;Chen et al 1997). Previously, Chambers et al (2002b) compared ADH genotype frequencies between alcoholics and nonalcoholics in a sample of young male native NZ Polynesians (M" aori).…”

Section: Introductionmentioning

confidence: 99%

Haplotype analysis at the alcohol dehydrogenase gene region in New Zealand Māori

2006

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Alcohol response is a genetically influenced trait, and there is significant variation in the patterns of alcohol consumption between M" aori and Caucasians in New Zealand. Previous studies have found that a variant of the alcohol dehydrogenase (ADH) gene (ADH1B*47His) is associated with protection against alcohol dependence in M" aori. Here we extend our investigation of the ADH genes, hypothesising a different haplotype signature in Maori compared to Caucasians. We analysed nine single nucleotide polymorphisms (SNPs) spanning a 500-kb region on chromosome 4q surrounding the ADH1B variant and several other alcohol-metabolising genes (ADH 4, 5, 6, 7). Genotyping was carried out on 47 unrelated M" aori individuals, and allele frequencies were compared to the Caucasian population. Large differences in minor allele frequencies were observed between M" aori and Caucasian populations for six SNPs (P < 0.01). There was also strong linkage disequilibrium (LD) observed among SNP alleles in Maori indicating the presence of extended ancestral haplotype blocks (P < 0.01). Our results suggest that the M" aori population has a different haplotype signature at the ADH gene region compared to Caucasians. These findings probably reflect the unique gene flow history of this genomic region in Maori and should be beneficial for designing future genetic association studies of alcohol-response traits and associated disorders in Polynesians.

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Alcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines

Cited by 76 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?

Acetaldehyde dehydrogenase 2 SNP rs671 and susceptibility to essential hypertension in Mongolians: a case control study

Haplotype analysis at the alcohol dehydrogenase gene region in New Zealand Māori

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