'Happyhour' gene may explain alcoholism

Posted by Emma Woollacott

Berkeley, CA - They're calling it the 'happyhour' gene - an explanation for why some of us are better able to handle our drink than others. It may explain why some people are more prone to alcoholism than others, and indicates that certain anti-cancer drugs could also help treat alcoholism.


Animals with a mutant version of the gene grow increasingly resistant to alcohol's sedative effects, the research shows. While the research was carried out on those famously party-loving creatures, fruitflies, the scientists say the happyhour gene is also present in humans. Several genes which play a role in fruit flies' alcohol response hold similar roles in mammals.


In the new study, the researchers screened mutant flies for those less sensitive to ethanol. That screen led them to happyhour, a gene closely related to mammalian enzymes known as the Ste20-family kinases of the GCK-1 subfamily.



The researchers found evidence that the gene normally does its work by blocking the so-called Epidermal Growth Factor (EGF) pathway. That EGF pathway is best known for its role in cancer, and drugs designed to inhibit the EGF receptor, including erlotinib (trade name Tarceva) and gefitinib (trade name Iressa), are FDA-approved for the treatment of non-small cell lung cancer.


Now, the researchers have shown that flies and mice treated with erlotinib also grow more sensitive to alcohol. What's more, rats given the cancer-fighting drug spontaneously consumed less alcohol when it was freely available to them. Their taste for another favourite tipple - sugar water - was unaffected.


"This is a very powerful example of how simple model organisms - and the little fruitfly in particular - can be used to move quickly from an unknown gene to a potential therapy for drug addiction," said Ulrike Heberlein of the University of California.


Human studies indicate that there's a strong genetic component to alcoholism, but identifying the specific genes responsible has proved tricky. Studies have also indicated that an individual's sensitivity to alcohol acts as a predictor of future alcoholism - the better your head for drink, the more likely you are to become an alcoholic.


Heberlein said they still don't know exactly how alcohol exerts its influence on the EGFR pathway or how exactly that leads to the all the symptoms of drunkenness that we know and love so well. Those questions will be the subject of future investigation. Her team is also exploring other new gene candidates that turned up in the fly screens. She says that several of those appear to be tied to the EGFR pathway in different ways.


"It's not yet clear how it all fits together," she said. "But the fact that we've come, in an unbiased way, to molecules in the same pathway is telling us this is really, really important."