Genes set the table for alcohol outcomes

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I quoted Shakespeare’s Hamlet in my last column who, after waxing on about “what a piece of work is man,” asks his friend Rosencrantz: “What is this quintessence of dust?”

“Dust to dust” is our eventual fate but, in the meantime, of what are we made? What is our essence?

Rodents and fruit flies offer some intriguing, if partial, answers to these questions.

Many years ago I read about the DBA and C3H strains of mice that consistently prefer water over alcohol when given a choice. The C57 and C58 breeds, however, choose alcohol over water almost every time.

The offspring of the alcohol-loving rodents inherit mom and pop’s fondness for booze, while the alcohol-hating mice produce litters that just don’t like the stuff.

A more recent study reveals that mice possessing a subtype of the Grm7 gene tend to drink more alcohol. Grm7 is involved in communication between brain cells in mice. The mutated form of the gene reduces messenger RNA, indicating that the brain’s glutamate pathways play an important role in reinforcement and addiction.

Okay, that’s more than you really wanted to know.

But here’s another good one. Rats that tend to like (“have a high preference for”) alcohol are more sensitive to stress and more likely to “reinstate alcohol-seeking behavior” when subjected to environmental stress.

These rats have higher levels of the stress-related gene crhr1 and when stressed, they start drinking heavily. This research speaks to the role of “epigenetics,” environmental influences such as diet, lifestyle, and trauma that can alter the expression of our genes and affect our vulnerability or resistance to disease. I’ll cover epigenetics in my next column.

Fruit flies get drunk, too. Researchers have discovered 23 fruit fly genes that have human equivalents, which means that the fruit fly research can be translated to the human population.

One particular gene makes fruit flies highly sensitive to alcohol — they get “drunk” on the equivalent of a glass of wine. Researchers labeled the gene “Cheapdate.”

In later studies the same researchers discovered a gene that raises tolerance for alcohol. They called this one “Happy Hour.”

The “hangover” gene in fruit flies appears to increase tolerance for alcohol, which means that fruit flies with the gene are able to drink more without getting drunk. And, of course, the more the little buggers drink, the greater the chance they’ll get addicted to the stuff.

Tolerance may seem like a great thing — you can just imagine a fruit fly bragging to its neighbor that it can drink the equivalent of a case of beer and still fly home — but flies (and humans) with lower tolerance (greater sensitivity) levels tend to be protected against addiction. One or two drinks and they’re grounded.

“Cheapdate,” “Happy Hour,” and “Hangover” genes — don’t you love it? And now for the “Lightweight” and “Lush” fruit flies.

In a 2007 study, researchers at North Carolina State University bred fruit flies over 25 generations into two groups — “lightweight” flies that were highly sensitive to the effects of alcohol and “lushes” that were highly tolerant.

Some 1,500 genes were linked to the difference between “lightweights” and “lushes,” and 32 mutated genes directly affected sensitivity to alcohol.

The testing method was ingenuous. Fruit flies were exposed to alcohol vapors through an “inebriometer,” a long vertical tube with platforms onto which the flies could cling. As the flies became inebriated, they fell from one platform to the next until they finally collapsed at the bottom of the tube.

The “lightweights” tumbled downward after just a minute or two of exposure to the vapors while the “lushes” were able to hang on for about 18 minutes.

Fruit flies, for all their light-weightedness, are infinitely and astonishingly complicated — much like the “quintessence of dust” called human beings.

So here’s my quick and dirty synopsis of the genetic research on addiction-related genes.

Maybe when someone starts talking about why Joe doesn’t just put the damn bottle down or why the heck Jane can quit using but relapses over and over again, we can keep these little gene stories in the back of our minds.

We’re not all the same. We’re not always in control. And we’re not — definitely not — perfect.

The genes tell us so.

Kathy Ketcham is the co-author of 14 books and executive director of Trilogy Recovery Community. For more information, go to www.trilogyrecovery.org.

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