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. 2010 Jan;332(1):202-9.
doi: 10.1124/jpet.109.159855. Epub 2009 Sep 28.

Nicotine metabolism in African Americans and European Americans: variation in glucuronidation by ethnicity and UGT2B10 haplotype

Jeannette Zinggeler Berg  1 , Jesse Mason, Angela J Boettcher, Dorothy K Hatsukami, Sharon E Murphy
Affiliations

Nicotine metabolism in African Americans and European Americans: variation in glucuronidation by ethnicity and UGT2B10 haplotype

Jeannette Zinggeler Berg et al. J Pharmacol Exp Ther. 2010 Jan.

Abstract

Nicotine is the major addictive agent in tobacco smoke, and it is metabolized extensively by oxidation and glucuronide conjugation. The contributions of ethnicity and UGT2B10 haplotype on variation in nicotine metabolism were investigated. Nicotine metabolism was evaluated in two populations of smokers. In one population of African American and European American smokers (n = 93), nicotine and its metabolites were analyzed in plasma and 24-h urine over 3 days while participants were abstinent and at steady state on the nicotine patch. In a second study of smokers (n = 84), the relationship of a UGT2B10 haplotype linked with D67Y to nicotine and cotinine glucuronidation levels was determined. We observed that both African American ethnicity and the UGT2B10 D67Y allele were associated with a low glucuronidation phenotype. African Americans excreted less nicotine and cotinine as their glucuronide conjugates compared with European Americans; percentage of nicotine glucuronidation, 18.1 versus 29.3 (p < 0.002) and percentage of cotinine glucuronidation, 41.4 versus 61.7 (p < 0.0001). In smokers with a UGT2B10 Tyr67 allele, glucuronide conjugation of nicotine and cotinine was decreased by 20% compared with smokers without this allele. Two key outcomes are reported here. First, the observation that African Americans have lower nicotine and cotinine glucuronidation was confirmed in a population of abstinent smokers on the nicotine patch. Second, we provide the first convincing evidence that UGT2B10 is a key catalyst of these glucuronidation pathways in vivo.

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Figures

Fig. 1.
Fig. 1.
Glucuronide conjugation pathways of nicotine metabolism.
Fig. 2.
Fig. 2.
Percentage of cotinine excreted as its glucuronide in 24-h urine by ethnicity.
Fig. 3.
Fig. 3.
In vitro nicotine glucuronide conjugation by UGT2B10 haplotype. Human liver microsomes were incubated with 0.5 mM [3H]nicotine (specific activity, 25 nCi/nmol) and 5 mM UDPGA.
Fig. 4.
Fig. 4.
Percentage of cotinine excreted as its glucuronide in 24-h urine by UGT2B10 genotype.
See this image and copyright information in PMC

References

    1. Benowitz NL. (1999) Nicotine addiction. Prim Care 26:611–631 - PubMed
    1. Benowitz NL, Jacob P, 3rd, Fong I, Gupta S. (1994) Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther 268:296–303 - PubMed
    1. Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, Jacob P., 3rd (1999) Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 291:1196–1203 - PubMed
    1. Benowitz NL, Pomerleau OF, Pomerleau CS, Jacob P., 3rd (2003) Nicotine metabolite ratio as a predictor of cigarette consumption. Nicotine Tob Res 5:621–624 - PubMed
    1. Caraballo RS, Giovino GA, Pechacek TF, Mowery PD, Richter PA, Strauss WJ, Sharp DJ, Eriksen MP, Pirkle JL, Maurer KR. (1998) Racial and ethnic differences in serum cotinine levels of cigarette smokers: Third National Health and Nutrition Examination Survey, 1988–1991. J Am Med Assoc 280:135–139 - PubMed

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