Abstract

Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, behind this red complexion lies a far more menacing problem. This alcohol flushing response is caused by the accumulation of acetaldehyde, a carcinogenic intermediate product of alcohol metabolism. In humans, the main enzyme responsible for breaking down harmful acetaldehyde into harmless acetate is aldehyde dehydrogenase 2 (ALDH2). ALDH2 deficiency, the result of a point mutation in the ALDH2 gene, produces a much less efficient ALDH2 enzyme. This leads to an accumulation of acetaldehyde and the subsequent flushing response. While about 8% of the global population is ALDH2 deficient, the prevalence of this issue is much higher in East Asia, where approximately 36% of East Asians possess this deficiency. In our home, Taiwan, approximately 47% of the population carries this genetic mutation--the highest percentage in the world. Depending on the amount of alcohol consumption, ALDH2 deficiency may increase the risk of developing esophageal cancer by up to 12 times and head and neck cancer by up to 8 times. Our project aims to produce recombinant ALDH2 in order to lower levels of acetaldehyde in the upper digestive tract region. We envision delivery of ALDH2, for instantaneous use, to be achieved in the form of a purified protein or in consumer-friendly probiotics such as lactobacillus. Alternatively, we also plan to regulate ALDH2 expression using an alcohol-induced promoter, pAlc, for a longer-term solution. Ultimately, we seek to produce a product to effectively combat the adverse health implications of ALDH2 deficiency.