How does gene expression affect ethanol metabolism?

It is thought that genetic variations in noncoding regions of both ADH and ALDH genes may play a role in influencing alcohol metabolism and, consequently, the risk of developing alcoholism. The expression of genes coding for these alcohol-metabolizing enzymes determines the rate at which ethanol is converted into acetaldehyde and then into acetate. The ADH gene family encodes for alcohol dehydrogenase enzymes, while the ALDH gene family codes for aldehyde dehydrogenase enzymes. Most variations in the ADH and ALDH genes involve changes in single DNA building blocks, known as single-nucleotide polymorphisms (SNPs). These SNPs can be categorized into two types: coding variations and noncoding variations. One of the most well-studied variations in alcohol-metabolizing enzymes is linked to the ALDH2 gene. The ALDH2 allele involves a change where lysine replaces glutamate at position 504. This substitution leads to the production of an ALDH2 enzyme that is nearly inactive, no longer capable of efficiently converting acetaldehyde to acetate during ethanol metabolism. Variations in noncoding regions of ADH genes have been identified as influencing the susceptibility to alcoholism. In particular, it was shown that noncoding variations within ADH4 are closely linked to the likelihood of developing alcoholism in European-American families.  

The CYP2E1 gene encodes for the cytochrome P450 2E1 enzyme, which is involved in the microsomal ethanol oxidizing system (MEOS) pathway. More specifically, the enzyme CYP2E1 metabolizes ethanol and various substrates. This process results in the formation of toxic metabolites and the generation of free radicals in the form of reactive oxygen intermediates, leading to liver damage and oxidative stress. In this pathway, CYP2E1 utilizes oxygen to oxidize ethanol into aldehyde and this reaction also involves the conversion of NADPH to it NADP+.