Question

Explain the genetic polymorphism associated with the metabolism of ethanol in persons of Asian descent.

Answer 1

1. There is a high individual variability in ethanol metabolism. These variability mainly due to variations in the main ethanol and acetaldehyde metabolising enzymes eg. ADH and ALDH
2. These genetic polymorphism determine the level of acetaldehyde accumulation after alcohol consumption.
3. The variant ADH2*2 allele is mostly seen in East Asian individuals but rare in non Asians.
4. There is an association between ADH polymorphism and risk of alcohol cirrhosis
5. The ADH2 gene is located in chromosome 4q21-q23 and there are several polymorphism sites in the ADH 2 gene
6. The beta2beta2 enzyme encoded by ADH2*2 is approximately 20 fold more active in ethanol oxidation than the beta1beta1 enzyme.
7. Individuals who inherited the ADH2*2 allele have homodimeric and heterodimeric beta2 containing isoenzymes and could be expected to have faster rate of alcohol metabolism and it leads to higher accumulation of acetaldehyde after consumption of alcohol.