DRD2 Ins was associated with alcoholism in those alcoholics who carried the ADH1B*2 or ADH1C*1 protective alleles (p = 0.032 in genotype level and p = 0.015 in allele level).
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.
There was evidence of association to alcohol dependence for seven adjacent markers spanning 98,000 bp in the middle and 3'-portion of the GABRA2 gene (range of P-values = 0.008-0.03).
Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration.
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).
Variants in GABRA2 have been associated with adult alcohol dependence as well as phenotypic precursors, including impulsiveness and externalizing behaviors.
We develop a pharmacokinetic model describing how genetic variations in ADH1B, ADH1C, ADH7, ALDH2, and TAS2R38 affect consumption behavior, and alcohol and acetaldehyde levels over time in various tissues of individuals with a particular genotype to predict their susceptibility to alcohol dependence.
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.
Genotyping of the 3 single nucleotide polymorphisms (SNPs) across the GABRA2 gene (rs567926, rs279858 and rs9291283) was performed in patients with alcohol dependence (N=654) and healthy control subjects (N=574).
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 study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004).
The region of strongest association with alcohol dependence extended from intron 3 past the 3' end of GABRA2; all 43 of the consecutive three-SNP haplotypes in this region of GABRA2 were highly significant.
Non-coding variations in GABRA2, the gene encoding the alpha2 subunit, are associated with the risk for alcoholism, suggesting that regulatory differences are important.
The ADH1C*2 allele was significantly associated with alcohol dependence overall and within Indo-TT ancestry, however, it was not associated with current or heaviest alcohol consumption levels.
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 key findings of the earlier studies were that variations (i.e., polymorphisms) in the DNA sequences of the genes encoding alcohol dehydrogenase 1B (i.e., the ADH1B gene), aldehyde dehydrogenase 2 (i.e., the ALDH2 gene), and other alcohol-metabolizing enzymes mediate the risk for alcoholism; moreover, these polymorphisms also have an impact on the risk of alcohol-related cancers, such as esophageal cancer.
The alcoholism-susceptibility genotype ADH1B*1/*1 was less frequent in the gastrectomy group, suggesting a competitive gene-gastrectomy interaction for alcoholism.
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.