Genes 'affect alcohol tolerance'

“'Tipsy' alcohol gene 'could help curb alcoholism'”, reads a BBC News headline. It said, “US researchers believe 10% to 20% of people have a version of the gene that may offer some protection against alcoholism.”

This story is based on a study of 238 college students and their siblings, which investigated how a person’s genes might affect how well they can tolerate alcohol. It found that a region of DNA containing the CYP2E1 gene is linked with alcohol tolerance. These findings will need to be confirmed in other studies.

The researchers report that previous studies have suggested that people with high alcohol tolerance may also be more likely to develop alcoholism. However, as this study did not look at alcoholism itself, it is not possible to say whether this gene is also linked with alcoholism. It is too early to suggest that “people could be given CYP2E1-like drugs to make them more sensitive to alcohol…to put them off drinking to inebriation” as suggested in the news.

Where did the story come from?

The study was carried out by researchers from the University of North Carolina and other research centres in the US and Australia. It was funded by the State of California, the Veterans Affairs Research Service, the National Institute on Alcohol Abuse and Alcoholism, the CompassPoint Addiction Foundation, and the Bowles Center for Alcohol Studies. The study was published in the peer-reviewed journal Alcoholism: Clinical and Experimental Research.

The story was covered by BBC News, the Daily Mail, Metro, and the Daily Express . The newspapers generally report the study's methods accurately. However, the possible practical applications of this study for alcoholism have been over-emphasised, with suggestions that the findings have direct implications for preventing or treating the condition.

What kind of research was this?

This was a genetic study in families, investigating how a person’s genes might affect how well they can tolerate alcohol.

The researchers say that one of the factors that affect a person’s likelihood of becoming an alcoholic is their early experiences with alcohol. Those who show a higher ‘tolerance’ during these first occurrences tend to drink greater amounts in the future. Here, they were interested in looking at what genes might affect a person’s response to alcohol (their alcohol tolerance).

The researchers had investigated this in two previous studies, one of which had suggested that a genetic region at the end of the long arm of chromosome 10 was associated with alcohol tolerance. This region contains the gene that produces the CYP2E1 protein, which is involved in breaking down alcohol as well as other chemicals. Variations in this gene could therefore potentially affect alcohol tolerance. This current study combined and re-analysed the samples that had been used in the two previous studies.

What did the research involve?

The researchers had initially enrolled 238 college students (aged 18 to 29 years old) and their siblings. All participants had reported having at least one alcohol-dependent parent, but were not alcohol-dependent themselves.

The researchers used a standard test and questionnaire to assess the participants’ alcohol tolerance. In the test, participants were asked to drink a standard amount of alcohol over an eight-minute period (0.75ml/kg for women and 0.9ml/kg for men using a 19% alcohol solution). Measurements of their breath alcohol levels, body swaying and questionnaire scores were taken before the alcohol was drunk. They were taken again at set times in the three hours afterwards. The researchers decided to use the response at one hour after drinking the alcohol as their indicator of alcohol tolerance.

The researchers examined 811 sites across the participants’ DNA, looking for any sites near genes that might be controlling alcohol tolerance. They were particularly interested in the region around the CYP2E1 gene. They used standard techniques to do this, which essentially involved looking for areas of DNA that are shared more often than would be expected by chance between siblings who have similar alcohol tolerance, and not shared between siblings with different alcohol tolerance. They also looked at 10 single ‘letter’ variations in and around the CYP2E1 gene to see if these were associated with alcohol tolerance.

Finally, they looked at the genetic code of the CYP2E1 gene in the 96 participants whose data showed the greatest evidence of a link between the CYP2E1 gene and alcohol tolerance, to see if they carried any variations that might affect the protein that the gene produced.

What were the basic results?

The results appeared to show that alcohol tolerance was linked to a genetic region at the end of the long arm of chromosome 10, which contains the CYP2E1 gene. This evidence was stronger once the researchers removed one family from their analysis whose alcohol tolerance results were thought to be unreliable. The genetic variation that showed the strongest link with alcohol tolerance could only explain 4.6% of the variability in people’s alcohol response questionnaire scores. These results suggested that none of the regions tested are likely to be the only regions affecting alcohol tolerance.

When the researchers looked at the families who showed the strongest evidence of a link between this gene and their alcohol tolerance, they could not find specific changes in the CYP2E1 gene sequence that would affect the protein that it produced, and therefore might affect alcohol tolerance. They suggested that this meant that variations in the nearby regions controlling the activity of the gene might be responsible instead of variations within the gene itself.

How did the researchers interpret the results?

The researchers conclude that genetic variations in or near the CYP2E1 gene “affect the level of response to alcohol providing a predictor of risk of alcoholism”. They say that the involvement of this gene “allows inferences to be made about how the brain perceives alcohol”.

Conclusion

This study has shown an association between the region containing the CYP2E1 gene and alcohol tolerance. These findings will need to be confirmed in other samples before any firm conclusions can be drawn. Importantly, the researchers could not identify any variations within the CYP2E1 gene that could potentially account for differences in alcohol tolerance. In addition, this region appears to account for only a small amount of the variation in people’s alcohol tolerance. This suggests that the majority of a person’s tolerance is explained by other factors (possibly genetic and environmental).

It is also important to note that although the researchers suggest that alcohol tolerance may affect risk of alcoholism, this study did not directly look at people who were alcohol dependent. Therefore they cannot say whether the CYP2E1 gene is also linked to alcoholism. Without further research, the current findings do not provide ways to predict or treat alcoholism.

Contrary to what might be suggested by the newspapers, genes were already known to play a role in how a person deals with alcohol. People who have certain variations in the genes which produce the alcohol dehydrogenase enzymes that break down alcohol are less able to tolerate alcohol. It is likely that environmental factors, such as previous exposure to alcohol, also play a role in a person’s alcohol tolerance.