Drunken Worms Could Help Decode Alcoholism Genetics

(Inside Science) -- Imagine a checkup with your physician that includes not only the standard blood work, body weight, and blood pressure, but also a test that screens whether your genetic makeup puts you at risk of developing an addiction to alcohol.

That’s the pursuit of geneticists and addiction experts.

It’s no simple task -- while scientists widely acknowledge that genetic mutations likely cause some cases of alcoholism, they haven’t identified a single gene as the culprit. In fact, it’s likely to be an interaction between several genes and gene complexes. There’s also the interplay between the environment and DNA to consider, which further muddies the water.

New research conducted at Virginia Commonwealth University, in Richmond, and published in the Proceedings of the National Academy of Sciences has uncovered a genetic variation that influenced alcohol tolerance in worms. The researchers said this gene variant could provide some clues in the hunt for genetic factors that put humans at risk of alcoholism.

The study authors gave ethanol to roundworms and watched through a microscope as the animals became drunk.

“We measured locomotion,” said Jill Bettinger , an associate professor of pharmacology and toxicology, and senior author of the study. “Intoxication slows and flattens the amplitude [distance] and decreases the frequency of their wave movements. We also assessed the speed of their crawl,” she added.

The deterioration of a worm’s locomotive capacity varied depending on the activation or inhibition of the genetic coding for a protein complex called “switching defective/sucrose non-fermenting” — or SWI/SNF for short, which is found in all animals.

The results indicated that the SWI/SNF genes in some worms might have made them more tolerant to the ethanol than others.

Tolerance, especially a person’s initial sensitivity to their first drink, is related to the risk of alcoholism onset, explained co-author Brien Riley , an associate professor of psychiatry and human and molecular genetics. “A low level of tolerance to alcohol has a protective element to it because you can’t drink so much,” he said.

Studies have shown a well-established trend that addiction correlates with the quantity of alcohol a person drinks, explained Riley. “The risk of dependence goes up with exposure,” he said. But that’s still not to say that people with low tolerance are at zero risk of developing an addiction.

“It’s like a buffer to alcohol -- part of dependence is that you develop a pharmacological tolerance to high doses,” explained David Lewis , a professor of alcohol and addiction studies at Brown University in Providence, Rhode Island.

Lewis, who is also a board member of the National Council on Alcoholism and Drug Dependence (NCADD), was not involved in the study.

NCADD lists tolerance as a symptom of alcoholism alongside craving, loss of control and withdrawal.

Scientists estimate that dodgy DNA could be responsible for about half of the population’s risk of developing alcoholism — studies have shown that the disease runs in families. Of course, that also raises the classic nature versus nurture question, and we can’t forget about the non-genetic factors, said Lewis.

“Alcoholism running in families could also depend on environmental things too,” said Lewis, “just like learning languages is familial, not genetic.”

But he added it’s generally accepted that both genetic and environmental factors contribute to an individual’s risk of becoming addicted to the drug.

It’s also marginally more likely that a father will pass on his alcoholism to his children than a mother, added Lewis.

Precisely how the SWI/SNF protein complex influences alcohol tolerance isn’t immediately clear, according to the study authors. But they do know that the proteins change how DNA is wrapped around its scaffold, and can therefore influence the activation of many other genes.

It’s likely to be one or more of these genes that are turned on or off by the complex that alters tolerance, but they aren’t yet sure which one.

Both Riley and Bettinger say their findings on worm tolerance to ethanol are likely to translate to human dependence on alcohol. DNA wrapping proteins like SWI/SNF are often shared across the animal kingdom, whether in a worm or human cell.

“Fundamentally, they’re not that different,” said Bettinger.

Lewis isn’t so sure.

“The jump from monkeys to humans is significant enough, so just think how different things are when we’re talking about worms,” he said. The key thing to understand with alcoholism is the relationship between genes and environmental factors, he added, and the environmental factors for a tiny worm and a human are poles apart.

Nevertheless, Bettinger hopes that the research gets medical science closer to understanding the genetic side of the disease, which means your doctor might be able to tell you go easy on the drinking if your genetic makeup puts you at risk. But it might also help with drug development .

“There are few and relatively ineffective pharmacological treatments,” said Bettinger. “If we understand the genetics of alcoholism then we have a better chance of rationally developing drugs.”