"ALDH2 is associated to alcohol dependence and is the major genetic determinant of ""daily maximum drinks"" in a GWAS study of an isolated rural Chinese sample."
"ALDH2 is associated to alcohol dependence and is the major genetic determinant of ""daily maximum drinks"" in a GWAS study of an isolated rural Chinese sample."
ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%, 7.9%, and 22.9% of phenotypic variation, respectively, in this sample.
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.
ALDH2*2 demonstrates its effect on alcohol consumption limiting and alcoholism developing protection, and this variant is recently found to have an important impact on human health.
A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism.
A point mutation in the aldehyde dehydrogenase 2 gene (ALDH2(2) allele) is considered to be a genetic deterrent for alcoholism; however, 80 of 655 Japanese alcoholics had the mutant allele.
A previous cross-sectional study showed that, among individuals of Chinese and Korean descent, possession of ALDH2*2 alleles was associated with protection against alcohol dependence, whereas conduct disorder was associated with increased vulnerability to dependence.
According to these results, not only ALDH2 gene, often claimed to be responsible for alcohol dependence among Japanese, but also ADH2 gene polymorphism, which modulates the metabolism of ethanol, play important roles in habitual alcohol intake behavior in Japanese patients and in some patients leads to alcoholic liver diseases.
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.
ADH(2), ADH(3), and CYP(450)2E1 Pst-I and Dra-I genetic variations are not related to alcoholism or susceptibility to alcoholic liver disease in our male population.ALDH(2) locus is monomorphic.
After stratification by the relevant genotypes of ADH2, ADH3, and ALDH2no significant association exists between the genetic variants at the DRD2 locus and alcoholism in the Chinese Han population.
Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) polymorphisms, specifically the ADH3*1, ADH2*2, and ALDH2*2 genotypes appear to confer a protective effect against alcoholism, most notably in Oriental subjects.
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).
Although preliminary, these results suggest that an inactive ALDH2-mediated delay in the occurrence of alcohol-related problems seems to contribute to the suppression of alcoholism development.
Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking.
Although the ALDH2*2 variant allele has been widely accepted as protecting against the development of alcoholism in Asians, the association of the ADH1B*2 variant allele with drinking behaviour remains inconclusive.
Among northeast Asians, the variant aldehyde dehydrogenase allele, ALDH2*2 (rs671, A/G, minor/major), has been inversely associated with alcohol dependence.
Associations among liver disease, serum lipid profile, body mass index, ketonuria, meal skipping, and the ADH1B and ALDH2 genotypes in Japanese men with alcohol dependence.
Because inactive ALDH2 is an established negative risk factor for alcoholism, alcoholics with the mutant allele, ALDH2*2, were considered a relatively homogeneous group.
Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence.
Data are consistent with the hypothesis that elevations in acetaldehyde, increased sensitivity to alcohol, and lower levels of drinking reflect the mechanism by which the ALDH2*2 allele reduces risk for alcohol dependence.