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article imageEssential Science: Zeroing in on a gene that stops you drinking

By Tim Sandle     Dec 5, 2016 in Science
A large study has pinpointed a gene variant that suppresses the desire of a person to drink alcohol. The next question is whether the discovery can be used for medicinal purposes.
The research, which took the form of a review of many other studies (a meta-analysis), was led by UT Southwestern Medical Center scientists. This took the form of mapping and comparing the genetics of more than 105,000 people. The people examined were classed as either ‘light’ or ‘heavy’ social drinkers, based on an assessment of the quantity and frequency of alcohol consumed.
These terms were interpreted as heavy drinkers consuming more than 21 drinks per week for men and 14 drinks per week for women; and light drinking as 14 drinks or less per week for men and seven drinks or less per week for women, with a drink being equivalent to half a pint of beer or a small glass of wine.
According to the lead researcher Dr. David Mangelsdorf: “the study identified a variation in the β-Klotho gene linked to the regulation of social alcohol consumption.” The gene variation was found in around 40 percent of the people surveyed and, when present, appeared to lead to behaviors whereby the people affected drank less alcohol and noted that they did not have strong feelings to want to drink a lot of alcohol or to drink regularly. This equated to those with the gene variant drinking 42 percent less than those without the variant, when various lifestyle and demographic factors were accounted for.
The importance of the gene has been examined in animal studies, where genetically engineered mice with and without the gene variant were offered water or alcohol. These studies reveal that the β-Klotho gene directs the production of the β-Klotho protein that forms part of a receptor complex in the brain, suppressing the desire to drink.
The gene functions via a feedback circuit that runs from the liver, which processes alcohol, to the brain. Thus the β-Klotho is a co-receptor for a hormone called FGF21. This hormone is secreted from the liver and implicated in macronutrient preference in humans. The reward feedback loop is not dissimilar from those involved with sugar cravings.
A woman is about to sample a rare scotch at a private tasting in the VIP lounge at Whisky Live 2015.
A woman is about to sample a rare scotch at a private tasting in the VIP lounge at Whisky Live 2015.
The implications of the research are important given the health and social concerns arising from excessive drinking, including health relate deaths. Illnesses associated with a high level of alcohol consumption include:
Cancers of the mouth, throat and breast,
Heart disease,
Liver disease,
Brain damage,
Damage to the nervous system.
Psychologically, there is considerable evidence that alcohol is addictive. For some people, this tendency is lower than others and here there appears to be a genetic reason.
The implications of the study are that it may be possible to develop a drug to regulate alcohol consumption. How effective this is would need to be demonstrated through tests. The human-side of the research looked at people who were classed as regular drinkers, not those who might be classed as alcoholics. A drug working on the principle of the gene variant, therefore, would be something to potentially stop a light social drinker becoming a heavy social drinker.
With this, another researcher, Professor Gunter Schumann, from the Institute of Psychiatry at King's College London, told the Daily Telegraph: "Our study reveals a previously unrecognized liver-brain pathway which regulates alcohol consumption in humans, and which could one day be targeted therapeutically to suppress consumption in problem drinkers.”
Such a drug would fall within the emerging medical field of pharmacogenetics, which studies how genes affect the responses to different drugs. This study was funded by the U.K. Medical Research Council, the European Commission and the Howard Hughes Medical Institute.
The study has been published in the PNAS journal, with the research paper headed “KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.”
This article is part of Digital Journal's regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Last week looked at the role of nitrogen in the diet and the impact upon gut health. The previous week we profiled how nanotechnology can help with the introduction of safer cosmetics.
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