Nicotine metabolism shows ethnic bias

A comparison of Latino, white, and Chinese-American smokers suggests that people of East Asian descent are apt to clear nicotine from their blood more gradually than the other smokers do, thereby staving off a craving for the next cigarette.

Researchers recruited 131 smokers–37 Chinese-Americans, 40 Latinos, and 54 whites–for the analysis. Each volunteer gave a blood sample before receiving an intravenous infusion of nicotine. The substance was labeled with deuterium atoms, a heavy form of hydrogen, to make it detectable in the blood.

After the injection, the participants provided 10 blood samples at specific intervals over the next 8 hours, then one per day for 4 days.

Nicotine is cleared from the blood by liver enzymes that convert it to its metabolite cotinine. Blood analysis showed that it took an average of 152 minutes for half the injected nicotine to degrade in the blood of the Chinese-Americans in this study. Nicotine’s half-life in whites and Latinos was 134 and 122 minutes, respectively. Slow metabolism of nicotine draws out its effects, says Neal L. Benowitz, a clinical pharmacologist at the University of California, San Francisco. He and his colleagues report their work in the Jan. 16 Journal of the National Cancer Institute.

In a second test, the researchers measured the smokers’ blood concentrations of cotinine. Knowing how fast each volunteer converted nicotine to cotinine, the team could estimate how much nicotine had been inhaled in a given period and then divide that figure by how many cigarettes each person had smoked in that time–arriving at an amount of nicotine absorbed per cigarette. The calculations showed that Chinese-Americans took in less nicotine from each cigarette than whites or Latinos. This indicates the Chinese-Americans smoke less intensely, Benowitz says.

“The technique the researchers use for looking at [nicotine] metabolism is superb,” says Rachel F. Tyndale, a pharmacogeneticist at the University of Toronto. The work is the first to show explicitly that people of Asian descent dispose of nicotine more slowly than others do and therefore need to smoke less to avoid withdrawal symptoms, she says.

The biological basis for the differences in nicotine metabolism could include variations in a gene that encodes an enzyme called CYP2A6, which converts nicotine into cotinine, Benowitz says. CYP2A6 is also one of the enzymes that activate cancer-causing agents called nitrosamines that are found in tobacco smoke.

Smokers who have two fully functional copies of the CYP2A6 gene smoke 7 to 10 more cigarettes per day than smokers who have only one, Tyndale and her colleagues previously reported. Other research indicates that some Asians harbor more enzyme-slowing variations in the CYP2A6 gene than whites do, which could be part of the reason that Asians smoke less and get less lung cancer, Benowitz suggests. But he expects that variations in CYP2A6 will ultimately explain only a portion of smoking behavior.

Psychologist Ovide F. Pomerleau of the University of Michigan in Ann Arbor agrees. What lies ahead, he says, “is genetic archaeology,” as scientists dig for other influential genes.

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