Researchers from the U.S. and Europe compared the genomes of 105,000 light and heavy social drinkers and found there's a gene variant that limits alcohol intake. Along with the gene, the specific neural pathway that regulates alcohol consumption behaviour was identified. Scientists believe that by influencing this mechanism with drugs, it's possible to make drinks less desirable, something which might help those struggling with alcohol addiction.
University of Texas Southwestern Medical Center researchers analyzed the genetic makeup of light and heavy social drinkers of European ancestry participating in nearly four dozen other large population studies worldwide. Each participant had provided samples for genetic screenings but also completed a questionnaire that assessed their drinking habits. Heavy drinking was defined as more than 21 drinks per week for men and more than 14 drinks per week for women.
The team identified the β-Klotho gene as being linked to the regulation of social alcohol consumption. The gene codes the production of the β-Klotho protein that forms part of a receptor complex in the brain with 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 β-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,” said Dr. David Mangelsdorf, Chair of Pharmacology at UT Southwestern.
A less frequent variant of β-Klotho, which occurred in 40 percent of the study's participants, was associated with the desire to consume less alcohol. Previously, the genetic influence on drinking was thought to be too insignificant. Modern tools allow scientists to survey large swaths of genomes, which, this time, show that the genes have their part to play.
Tests on mice that were engineered to lack the β-Klotho gene variant showed the rodents preferred alcohol when offered a choice between water and alcohol. The preference remained even when the mice were given the hormone FGF21, which previous studies showed it acts on brain pathways to reduce cravings for sugar. The experiment concludes FGF21’s ability to suppress the preference for alcohol depends on the presence of β-Klotho.
“This is a hormone with some remarkable pharmacologic effects,” Dr. Mangelsdorf said. “The current study suggests that the FGF21-β-Klotho pathway regulates alcohol consumption in humans and seems to point to a mechanism that we might be able to influence in order to reduce alcohol intake.”
Worldwide, excessive alcohol consumption is a public health hazard that contributes to three million premature deaths every year. High blood pressure and obesity are among the risks associated with alcohol consumption.
Most research focuses on alcohol addiction, however, there are many people who hurt themselves with alcohol without being essentially addicted. A shift from heavy to moderate social drinking could have major public health benefits, such as reduced cardiovascular disease risk. Of course, people drink for a wide range of reasons but a β-Klotho-targeting drug could at least help with the physical urge to drink.
