Nicotine metabolism among African American and white smokers: Group and intraindividual differences in glucuronidation

It has long been known that African-American smokers have a harder time giving up cigarettes, and now researchers from the University of Minnesota may have found a potential biochemical explanation.

Investigators discovered that African-American smokers may have significantly lower levels of an enzyme that metabolizes nicotine and nicotine by-products, compared to Caucasians who were exposed to identical nicotine patches. The findings suggest that African Americans may experience higher nicotine levels per cigarette, which would help explain why “quit” rates are lower among this group.

“Smokers adjust their level of smoking to maintain blood levels of nicotine, which are determined in part by rates of nicotine metabolism, and while we can’t say from this study that differences in metabolism definitively account for lower quit rates, it could very well have an impact,” said Jeannette Zinggeler Berg, an M.D./Ph.D. student in Biochemistry, Molecular Biology, and Biophysics at the University of Minnesota.

In past studies, elevated levels of the nicotine-related molecule, cotinine, have been observed in African-American smokers compared to Caucasian smokers. Cotinine is a direct metabolite of nicotine – a product of nicotine metabolism – and so it is a marker for exposure to tobacco, Berg says. “It is not carcinogenic and is not an addictive component of tobacco, but the more of it a person has in their blood, the more nicotine they have been exposed to,” Berg said.

But researchers have debated whether differences in cotinine seen in African Americans is due to the common use of menthol cigarettes by the group, or to the fact that these smokers may be getting more nicotine per cigarette because they are smoking longer or inhaling more deeply.

In this study, Berg and her colleagues examined different markers of nicotine metabolism in 95 daily smokers who, during the study period, were required not to smoke and to wear a nicotine patch. They specifically looked at levels of glucuronides, which represent a pathway by which the liver metabolizes nicotine and cotinine, preparing these chemicals for urinary excretion. A low blood level of glucuronide can indicate an inefficient excretion pathway for nicotine, cotinine, and other substances such as pharmaceutical drugs, Berg says.

At the beginning of the study and after the participants started using the patch, nicotine metabolites were measured in urine samples. Both when subjects were smoking (baseline urine sample at the start of the study) or when they were on the nicotine patch, the percentage of cotinine in the glucuronide form was significantly lower among African Americans compared to Caucasian participants (at the start of the study: 66 percent versus 82 percent; on patch: 41 percent versus 62 percent). Glucuronidation of nicotine was also lower among African Americans compared to white participants on the patch (16 percent versus 30 percent).

“The higher levels of free cotinine seen in past studies between race groups could be explained by lower levels of glucuronide, which helps break down cotinine,” Berg said. “If cotinine is a marker of nicotine in the blood, people with higher levels are more likely to have trouble giving up cigarettes.”

Researchers are continuing the study by examining racial variation in two glucuronide enzymes in liver samples. “The differences we have seen could be explained by a number of factors, including environmental causes, and we hope to tease these influences apart,” Berg said.

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