Data presented show that antialcohol drugs that inhibit Aldh2 gene expression can be generated endogenously in liver cells infected by an adenoviral vector carrying an antisense-coding gene, thus mimicking the high-acetaldehyde phenotype that exists in humans carrying the Glu487Lys mutation who are protected against alcoholism.
Additionally, ALDH2 is involved in the elimination of metabolites of neurotransmitters like 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycoaldehyde (DOPGAL) in the central nervous system (CNS).<b>Areas covered</b>: We examine the role of ALDH2 polymorphism in disease, aging and alcohol addiction and discuss its pharmacological targeting.
All 3 traits showed genomewide significant association with variants near ALDH2, with significance ranging from 2.01 × 10<sup>-14</sup> (for flushing; lead single nucleotide polymorphism (SNP) PTPN11* rs143894582) to p<sub>meta</sub> = 5.80 × 10<sup>-10</sup> (for alcohol dependence criterion count; lead SNP rs149212747).
We find that disulfiram (Antabuse), an ALDH2 inhibitor in widespread clinical use for the treatment of alcoholism, selectively eliminates BRCA1/2-deficient cells.
Trends in gastrectomy and ADH1B and ALDH2 genotypes in Japanese alcoholic men and their gene-gastrectomy, gene-gene and gene-age interactions for risk of alcoholism.
Reduction in activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) enzyme due to genetic deficiency causes reactions related to alcohol consumption and lowers the risk of alcoholism.
In this report we determined the genotypes for three genes, ADH2, ADH3, and ALDH2 among subjects with alcohol dependence (n = 159) and ethnically matched normal controls (n = 149) for the four largest aboriginal groups (Atayal, Ami, Bunun, and Paiwan) in Taiwan.
Because inactive ALDH2 is an established negative risk factor for alcoholism, alcoholics with the mutant allele, ALDH2*2, were considered a relatively homogeneous group.
The alcoholics had significantly lower frequencies of the ADH2*2, ADH3*1, and ALDH2*2 alleles than did the nonalcoholics, suggesting that genetic variation in both ADH and ALDH, by modulating the rate of metabolism of ethanol and acetaldehyde, influences drinking behavior and the risk of developing alcoholism.
The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2.
The ALDH2*2 variant is associated with partial protection against alcohol dependence but confers significantly increased risk for alcohol-related cancers as a function of alcohol exposure.
We investigated whether variation in genes encoding cytochrome P450 2E1 (CYP2E1) or acetaldehyde-metabolising enzymes (ALDH1A1, ALDH2) might alter the risk of AD, with and without symptoms of anxiety, in a Cape population with mixed ancestry.
The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2*1 alleles and the risk of alcoholism (OR = 1.89 [95% CI 1.56-2.28], 1.32 [95% CI 1.12-1.57], and 4.35 [95% CI 3.04-6.23], respectively).
Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) affect susceptibility to alcoholism and may affect body weight via gene-associated differences in fuel utilization in alcoholics.
Individuals who are homozygous for polymorphism in ALDH2 tend to refrain from drinking alcohol, decreasing their chances of developing alcoholism and exposure to the associated risks.
Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism.
ALDH2rs671 polymorphism is proven to be closely related to the prevalence of CAD, hypertension, diabetes mellitus and alcoholism, which are etiological factors of heart failure.
We hypothesized that the ADH1B and ALDH2 genes might interact with the DRD2 gene and that the association between the DRD2 gene and alcohol dependence might be affected by different ADH1B and ALDH2 genotypes.
Logistic regression analyses of the remaining six combinatorial genotypes of the polymorphic ADH2 and ALDH2 loci indicated that individuals carrying one or two copies of ADH2*2 and a single copy of ALDH2*2 had the lowest risk (ORs 0.04-0.05) for alcoholism, as compared with the ADH2*1/*1 and ALDH2*1/*1 genotype.