Tackling Alcoholism with Gene Therapy and Chromatography

Alcohol is ubiquitous in modern society, there is no getting away from it. For many people this isn’t a problem — but for some, it leads to a premature death. The UK statistics around alcohol are quite frightening. Alcohol-related hospital admissions have doubled in a decade ago to over one million admissions per year. Alcohol-related deaths have also increased significantly in the period between 1994 and 2013.

The financial costs are harder to measure, but even allowing for discrepancies between different studies, the costs are damning. It is estimated that the total social cost of alcohol to England is up to £50 billion per year. But the individual costs can be even higher with lost and wasted lives resulting from alcohol addiction. But, new research published in the journal Human Gene Therapy suggest that gene therapy could help reduce the impact of alcoholism on society.

Genes for breakdown

For some people, drinking alcohol can bring about intense nausea — and I’m not talking about the reaction to drinking yourself stupid. Some people contain a variation in a gene that is involved in breaking down the ethanol in our drinks. The variation is prevalent in many people of East Asian origin including Chinese, Japanese and Koreans. People who have the variant suffer a condition known as Asian flush reaction — red face, nausea, dizziness and headache are just a few of the symptoms when they drink alcohol.

The reason for the reaction is down to how our bodies process and metabolize ethanol. When we drink, our livers metabolize ethanol in two steps that are controlled by enzymes. First, the enzyme alcohol dehydrogenase (ADH) breaks down ethanol into acetaldehyde. Then, the enzyme aldehyde dehydrogenase 2 (ALDH2) metabolizes the acetaldehyde into acetic acid, or vinegar.

Gene variants cause red faces

The Asian flush reaction is due to a variation in the ALDH2 gene (known as ALDH2*2). This variation affects the enzyme that breaks down the acetaldehyde, with the effect that the acetaldehyde is not efficiently broken down into acetic acid. This causes a build-up of acetaldehyde in the body which produces the red face and other symptoms. The symptoms are so unpleasant that many people with the variation avoid alcohol.

So, what if we could mimic the effect in people who suffer from alcoholism? Well, the team behind the research published in Human Gene Therapy modified the ALDH2 gene and delivered it to human liver cells. Ethanol was added to the cells a few days later, and then the acetaldehyde and ethanol levels were analysed by gas chromatography.

The use of GC to analyse volatiles like alcohol is discussed in the article, A New Method for Fast Residual Solvents Analysis and Untargeted Unknown Identification Faster Sample Throughput and Shorter GC Runtimes Using GC-VUV and Static Headspace. The researchers found that the acetaldehyde levels were raised in the cells with the adulterated gene — which suggests that the treatment could be a useful tool in the treatment of alcoholism.