Mar 06, 2024
ALCOHOL METABOLISM
Alcohol is absorbed from the stomach and intestines, and less than 10% of the absorbed alcohol is excreted through breath, sweat and urine. More than 90% of the absorbed alcohol circulates in the body and is transported to the liver via the portal vein. The liver has an important role in alcohol metabolism, as enzymes that metabolize alcohol are found at high levels in the liver. First, alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH), a primary enzyme that converts alcohol to acetaldehyde. Acetaldehyde is then rapidly converted to acetate by aldehyde dehydrogenase (ALDH). Acetate is metabolized to carbon dioxide (CO2), fatty acids (FA), and water (H2O) in peripheral tissues, not in the liver (Hyun et al., 2021).
What is the ADH1B Gene?
Other enzymes of Phase 1, Alcohol dehydrogenase (ADH) and Aldehyde dehydrogenase (ALDH), are involved in alcohol metabolism. These enzymes are involved in the formation of acetaldehyde from alcohol and the subsequent formation of acetic acid. Polymorphisms in the genes of this enzyme cause changes in alcohol tolerance levels in individuals (Xu et al., 2015).
Genetic variation in the ADH1B gene determines the rate at which ethanol is metabolized to acetaldehyde (Edenberg et al., 2018). The conversion of Arg48 to His48 occurs by substituting the adenine (A) allele for the guanine (G). This change (Arg48His) leads to an approximately 40-fold increase in the enzymatic activity of alcohol dehydrogenase, and as a result, the negative effects of alcohol consumption, such as nausea or abdominal pain, are felt more quickly (Edenberg et al., 2007).
rs1229984 is a single nucleotide polymorphism (SNP) in the ADH1B gene, which encodes a subunit of the alcohol dehydrogenase enzyme, an important catalyst in hepatic ethanol metabolism. The T/A allele of this SNP increases the activity of the enzyme, accelerating the metabolism of alcohol to acetaldehyde, a toxic byproduct. High acetaldehyde levels can cause symptoms such as facial flushing, nausea, and high heart rate (Rancelis et al., 2023).
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PHASE 1- Alcohol Sensitivity |
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Genes |
rs-code |
Minor Allele |
Minor Allele Description |
Reference |
|
ADH1B |
rs1229984 |
A |
Increased relative risk for alcohol intolerance |
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The table above contains the alcohol sensitivity gene and its polymorphism. This polymorphism affects a person's alcohol tolerance. In a study, It has been observed that people carrying the A allele in the ADH1B gene rs1229984 Arg48His polymorphism have low alcohol tolerance (Xu et al., 2015). In the study conducted by Thomasson et al. on alcohol addicts and non-alcoholic individuals, it was found that the rs1229984 polymorphism A allele was more common in individuals who were not alcohol dependent. The rs1229984 polymorphism A allele may have a protective role against alcohol dependence (Thomasson et al., 1991).
REFERENCES
Edenberg HJ, McClintick JN. Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review. Alcohol Clin Exp Res. 2018 Dec;42(12):2281-2297. doi: 10.1111/acer.13904. Epub 2018 Nov 11. PMID: 30320893; PMCID: PMC6286250. https://pubmed.ncbi.nlm.nih.gov/30320893/
Edenberg HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007;30(1):5-13. PMID: 17718394; PMCID: PMC3860432. https://pubmed.ncbi.nlm.nih.gov/17718394/
Hyun, J., Han, J., Lee, C., Yoon, M., & Jung, Y. (2021). Pathophysiological Aspects of Alcohol Metabolism in the Liver. International Journal of Molecular Sciences, 22(11). https://doi.org/10.3390/ijms22115717
Rancelis, T., Domarkiene, I., Ambrozaityte, L., & Utkus, A. (2023). Implementing Core Genes and an Omnigenic Model for Behaviour Traits Prediction in Genomics. Genes, 14(8), 1630. https://doi.org/10.3390/genes14081630 . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454355/
Thomasson HR, Edenberg HJ, Crabb DW, Mai XL, Jerome RE, Li TK, Wang SP, Lin YT, Lu RB, Yin SJ. Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am J Hum Genet. 1991 Apr;48(4):677-81. PMID: 2014795; PMCID: PMC1682953. https://pubmed.ncbi.nlm.nih.gov/2014795/
Xu, K., Kranzler, H. R., Sherva, R., Sartor, C. E., Almasy, L., Koesterer, R., Zhao, H., Farrer, L. A., & Gelernter, J. (2015). Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans. Alcohol Clin Exp Res, 39(7), 1137-1147. https://doi.org/10.1111/acer.12751