Researchers have identified a gene variant that suppresses the desire to drink alcohol, an advance that could lead to development of drugs to regulate alcohol consumption. The findings are based on the largest genome-wide association meta-analysis and replication study to date, mapping and comparing the genetics of over 105,000 light and heavy social drinkers, researchers said. "The study identified a variation in the beta-Klotho gene linked to the regulation of social alcohol consumption. The less frequent variant - seen in approximately 40 per cent of the people in this study - is associated with a decreased desire to drink alcohol," said Dr David Mangelsdorf, from The University of Texas Southwestern Medical Centre in the US. "Excessive alcohol consumption is a major public health problem worldwide, causing more than 3 million deaths per year," said Steven Kliewer, a Professor at UT Southwestern Medical Center. Researchers worked on beta-Klotho and the liver hormone fibroblast growth factor 21 (FGF21) that binds to the beta-Klotho-FGF21 receptor complex. They conducted experiments in mice to better understand the role of beta-Klotho in alcohol drinking behaviour. The beta-Klotho gene directs the production of the beta-Klotho protein that forms part of a receptor complex in the brain. The study could lead to development of drugs to regulate alcohol consumption - possibly even in those with drinking problems, researchers said. A shift from heavy to moderate social drinking could have major public health benefits, such as reduced cardiovascular disease risk, they said. The study compared the genetics of light and heavy social drinkers of European ancestry participating in nearly four dozen other large population studies worldwide. In addition to providing samples for genetic analysis, the participants answered questionnaires on their weekly drinking habits. Heavy drinking was defined as more than 21 drinks per week for men and over 14 drinks per week for women.
Light drinking was considered to be 14 drinks or less per week for men and seven drinks or less per week for women. The beta-Klotho gene codes for the protein beta-Klotho, which forms a receptor complex in the central nervous system (the brain and spinal cord) with classic receptors for FGF21, a hormone produced in the liver. "The gene in the current study seems to work via a feedback circuit that goes from the liver, which processes alcohol, to the brain, where beta-Klotho and classic FGF21 receptors form a cellular machine, or receptor complex, which binds to the liver hormone FGF21 to signal the response to alcohol," Mangelsdorf said. The less common gene variant identified in this study is related to a decreased desire for alcohol. So, people who have this variant tend to drink less than those without it, he said. The study was published in the journal PNAS.
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