Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking

Abstract

Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism is a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers.

Variation in CYP2A6 Activity and Personalized Medicine

“…Consistent with these higher frequencies, African Americans exhibit significantly lower non-renal clearance of cotinine compared to White individuals [ 54 ], suggestive of slower metabolism, mediated by CYP2A6. This is supported by a separate observation of lower overall CYP2A6 enzyme activity (measured by plasma NMR) among African American compared to White smokers [ 55 ]. Compared to White individuals, African American adolescent (ages 13–17) smokers also have significantly slower CYP2A6 activity (lower salivary NMR) [ 53 ].…”

Low Cotinine Glucuronidation Results in Higher Serum and Saliva Cotinine in African American Compared to White Smokers

“…In the studies presented here, we have confirmed this hypothesis, since when either saliva or serum cotinine levels are adjusted for both smoking dose and UGT2B10-catalyzed cotinine glucuronidation there is no longer any difference between the concentrations in African American and White smokers. Recently, reduced P450 2A6 activity has been proposed as the explanation of higher plasma cotinine in African American smokers (19,24,25). However, there is little data to support this.…”

Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer

“…The use of a more sensitive biomarker of tobacco consumption, such as TNE, may in the future allow us to detect subtle differences in smoking among these two light smoking populations. Moreover, titration of nicotine intake by CPD according to rate of nicotine metabolism may not be observed in these AI/AN populations, similarly to African American smokers [18, 60], but titration may be detected with TNE as measure of consumption, as seen among Alaska Native smokers [17]. …”