In the largest study of its kind, University of Texas (UT) Southwestern Medical Center researchers and colleagues in Europe have identified a gene variant that suppresses the desire to drink alcohol. “The findings are based on the largest genome-wide association meta-analysis and replication study to date, mapping and comparing the genetics – the DNA – of more than 105,000 light and heavy social drinkers,” said Dr. David Mangelsdorf, Chair of Pharmacology at UT Southwestern and a corresponding author of the study. “The study identified a variation in the β-Klotho gene linked to the regulation of social alcohol consumption. The less frequent variant – seen in approximately 40 percent of the people in this study – is associated with a decreased desire to drink alcohol,” he said. Dr. Mangelsdorf runs a laboratory with Dr. Steven Kliewer, another corresponding author of the study which was published online on November 28, 2016 in PNAS. “Excessive alcohol consumption is a major public health problem worldwide, causing more than 3 million deaths per year,” said Dr. Kliewer, a Professor of Molecular Biology and Pharmacology who holds the Nancy B. and Jake L. Hamon Distinguished Chair in Basic Cancer Research at UT Southwestern. “Much of the research on alcohol consumption has focused on addiction. However, the overall burden of alcohol-associated disease reflects the total amount of alcohol consumed, not just addiction.” The European research group knew that the UT Southwestern team had worked on β-Klotho and the liver hormone fibroblast growth factor 21 (FGF21) that binds to the β-Klotho-FGF21 receptor complex. “They asked us to conduct experiments in mice to better understand the role of β-Klotho in alcohol drinking behavior,” Dr. Mangelsdorf said.
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