title: Low Cotinine Glucuronidation Results in Higher Serum and Saliva Cotinine in African American Compared to White Smokers.
abstract: Background:Tobacco exposure is often quantified by serum or saliva concentrations of the primary nicotine metabolite, cotinine. However, average cotinine concentrations are higher in African Americans (AA) compared with Whites with similar smoking levels. Cotinine is metabolized by UGT2B10 and CYP2A6, and low UGT2B10 activity is common in AA, due to the prevalence of aUGT2B10splice variant.Methods:UGT2B10 activity was phenotyped in 1,446 smokers (34% AA) by measuring the percentage of cotinine excreted as a glucuronide. Urinary total nicotine equivalents (TNE), the sum of nicotine and 6 metabolites, were determined to quantify smoking dose, and cotinine and 3'-hydroxycotinine were quantified in saliva (study 1) or serum (study 2).Results:Ninety-seven smokers (78% AA) were null for UGT2B10 activity, and the saliva and serum cotinine levels, after adjustment for TNE and cigarettes per day (CPD), were 68% and 48% higher in these smokers compared with nonnull smokers (P< 0.001). After adjustment for TNE and CPD, salivary cotinine was 35% higher, and serum cotinine 24% higher in AA versus White smokers, but with additional adjustment for UGT2B10 activity, there were no significant differences in saliva and serum cotinine concentrations between these two groups.Conclusions:UGT2B10 activity significantly influences plasma cotinine levels, and higher cotinine concentrations in AA versus White smokers (after adjustment for smoking dose) result from lower levels of UGT2B10-catalyzed cotinine glucuronidation by AA.Impact:UGT2B10 activity or genotype should be considered when using cotinine as a tobacco exposure biomarker, particularly in populations such as AA with high frequencies ofUGT2B10nonfunctional variants.Cancer Epidemiol Biomarkers Prev; 26(7); 1093-9. ©2017 AACR.
authors.affiliation: Department of Biochemistry Molecular Biology and Biophysics and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. murph062@umn.edu.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Murphy
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sipe
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Kwangsoo
authors.initials: K
authors.lastname: Choi
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Raddatz
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Koopmeiners
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.affiliation: Masonic Cancer Center and Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
mesh_terms: D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D015415:Biomarkers / Q000032:analysis; D003367:Cotinine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6 / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D020719:Glucuronides / Q000378:metabolism / Q000652:urine; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism / Q000652:urine; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D065667:Renal Elimination; D012463:Saliva / Q000737:chemistry*; D000074285:Smokers / Q000706:statistics & numerical data*; D012907:Smoking / Q000097:blood* / Q000378:metabolism / Q000652:urine; D014481:United States; D044465:White People / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; D020719:Glucuronides; D020033:Protein Isoforms; C001381:hydroxycotinine; D009538:Nicotine; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; C552162:UGT2B10 protein, human; D014453:Glucuronosyltransferase; D003367:Cotinine