Exploring a genetic link to smoking

Science News, March 7, 1998 by Nathan Seppa

Dopamine, a chemical essential to brain function, has a reputation for being the life of the party Dopamine's day job is to act as a neurotransmitter, passing messages between nerve cells. However, when a person ingests substances that induce pleasure--such as nicotine, alcohol, cocaine, opiates, or even food--extra dopamine is released, enhancing the effect.

Now, researchers at the University of Texas in Houston studying nicotine suggest that an individual's genetic makeup may influence the impact of this dopamine reward. Their findings could help explain why quitting smoking is easy for some people and difficult for others.

Dopamine exerts its effects through receptor molecules in the brain. One gene encoding such receptors has components called A and B, each of which comes in two forms. These components, which are inherited, always occur in pairs. The A variation appears as A1A1, A1A2, or A2A2, and a similar pattern holds for the B variation.

The Texas researchers took blood samples from 283 people, 157 of whom had recently been diagnosed with lung cancer, to determine which genes they possess. Overall, 37 percent of the participants smoked.

The dopamine receptor genes appear to be linked to smoking habits. People with A1 or B1 in their genetic makeup started smoking a year earlier, on average, than those with A2A2 or B2B2, the researchers report in the March 4 Journal of the National Cancer Institute.

Smokers with an A1 or B1 version of the gene also reported few serious attempts to quit, says coauthor Margaret R. Spitz. Those showing A1. averaged four attempts and those with B1 averaged six attempts, compared to eight for their A2-only and B2-only counterparts.

Of 76 people in the study who had a B1 gene, less than 3 percent had never smoked. Among 193 people with the B2B2 pairing, 13 percent had never smoked.

Earlier research showed that roughly 10 percent of the U.S. population has a pairing that includes either A1 or B1. "This raises an interesting question: Are these people so genetically affected that they have a great problem quitting smoking?" asks Ernest P. Noble of the University of California, Los Angeles Medical Center.

While that question remains unanswered, the study supports the earlier hypothesis that people with A1 or B1 have fewer dopamine receptors, says Spitz. Such people experience a deficiency in the natural dopamine effect, making the reward from nicotine or other drugs more pronounced, Noble argues. He adds that this dopamine receptor gene "is not a smoking gene per se but a pleasure