Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population

@article{Mulligan2003AllelicVA,
  title={Allelic variation at alcohol metabolism genes (ADH1B,
ADH1C, ALDH2) and alcohol dependence in an American Indian population},
  author={Connie J. Mulligan and Robert W. Robin and Michael V. Osier and Nyamkhishig Sambuughin and Lev G. Goldfarb and Rick A. Kittles and Diane R. Hesselbrock and David Goldman and Jeffrey C Long},
  journal={Human Genetics},
  year={2003},
  volume={113},
  pages={325-336}
}
AbstractEnzymes encoded by two gene families, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), mediate alcohol metabolism in humans. Allelic variants have been identified that alter metabolic rates and influence risk for alcoholism. Specifically, ADH1B*47His (previously ADH2-2) and ALDH2-2 have been shown to confer protection against alcoholism, presumably through accumulation of acetaldehyde in the blood and a resultant 'flushing response' to alcohol consumption. In the current… 
The Genetics of Alcohol Metabolism
TLDR
These variants have been shown to influence a person's drinking levels and, consequently, the risk of developing alcohol abuse or dependence and people carrying certain ADH and ALDH alleles are at significantly reduced risk of becoming alcohol dependent.
Association of ADH and ALDH genes with alcohol dependence in the Irish Affected Sib Pair Study of alcohol dependence (IASPSAD) sample.
TLDR
The significant interaction effects between markers in ADH and ALDH genes suggest possible epistatic roles between alcohol metabolic enzymes in the risk for AD.
The Genetics of Alcohol Metabolism: Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants
  • H. Edenberg
  • Medicine
    Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism
  • 2007
TLDR
It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.
ADH and ALDH Polymorphisms and Alcohol Dependence in Mexican and Native Americans
TLDR
Polymorphisms in ADH1B are protective against alcoholism inThese two populations; however, these findings do not explain the high prevalence of alcoholism in these populations.
Association and ancestry analysis of sequence variants in ADH and ALDH using alcohol‐related phenotypes in a Native American community sample
  • Q. Peng, I. Gizer, C. Ehlers
  • Medicine
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2014
TLDR
Variants in or near ADH7 were significantly negatively associated with alcohol‐related phenotypes, suggesting a potential protective effect of this gene, and results suggested that a higher degree of NA ancestry is associated with higher frequencies of potential risk variants and lower frequencies of potentially protective variants for alcohol dependence phenotypes.
Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample.
TLDR
Variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence and haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype.
Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence.
TLDR
Several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the associations were best explained by several independent risk genes.
Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.
TLDR
To the authors' knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results suggest that higher blood Et OH andacetaldehyde concentrations in ADH 1B* 2/*2 may constitute the mechanism of protection against alcoholism by ADH2B*1*2/*2.
Alcohol and Aldehyde Dehydrogenase Polymorphisms in Chinese and Indian Populations
TLDR
The results showed that frequencies of ADH1B**2 and ALDH2**2 were higher in controls compared to alcohol-dependent subjects for both Chinese and Indians, and could explain the lower rate of alcohol dependence in Chinese.
Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis.
TLDR
There was strong evidence that variations in ADH4 are associated with alcoholism: 12 SNPs were significantly associated and the region of strongest association ran from intron 1 to 19.5 kb beyond the 3' end of the gene.
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