TY - JOUR
T1 - UGT2B10 genotype influences serum cotinine levels and is a primary determinant of higher cotinine in African American Smokers
AU - Sipe, Christopher J.
AU - Koopmeiners, Joe
AU - Donny, Eric C.
AU - Hatsukami, Dorothy K.
AU - Murphy, Sharon E.
N1 - Funding Information:
Research reported in this article was supported by the National Institute on Drug Abuse and FDA Center for Tobacco Products (U54 DA031659 to E.C. Donny, D.K. Hatsukami, and S.E. Murphy).
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/8
Y1 - 2020/8
N2 - BACKGROUND: Cotinine is the most widely used biomarker of tobacco exposure. At similar smoking levels, African Americans have higher serum cotinine than Whites. UGT2B10-catalyzed cotinine glucuronidation impacts these levels, and African Americans often have low UGT2B10 activity due to a high prevalence of a
UGT2B10 splice variant (rs2942857).
METHODS: Two
UGT2B10 SNPs (rs6175900 and rs2942857) were genotyped in 289 African Americans and 627 White smokers. Each smoker was assigned a genetic score of 0, 1, or 2 based on the number of variant alleles. Total nicotine equivalents (TNE), the sum of nicotine and six metabolites, and serum cotinine and 3'-hydroxycotinine were quantified. The contribution of
UGT2B10 genetic score to cotinine concentration was determined.
RESULTS: Serum cotinine was significantly higher in smokers with
UGT2B10 genetic scores of 2 versus 0 (327 ng/mL vs. 221 ng/mL;
P < 0.001); TNEs were not different. In a linear regression model adjusted for age, gender, cigarettes per day, TNE, race, and CYP2A6 activity, geometric mean cotinine increased 43% between genetic score 2 versus 0 (
P < 0.001). A 0.1 increase in the CYP2A6 activity ratio, 3'-hydroxycotinine/cotinine, resulted in a 6% decrease in cotinine. After adjustment for
UGT2B10 genotype and the other covariants, there was no significant difference in serum cotinine by race.
CONCLUSIONS:
UGT2B10 genotype is a major contributor to cotinine levels and explains the majority of high serum cotinine in African American smokers.
IMPACT: Cotinine levels in smokers may greatly overestimate tobacco exposure and potentially misinform our understanding of ethnic/racial difference in tobacco-related disease if
UGT2B10 genotype is not taken into account.
AB - BACKGROUND: Cotinine is the most widely used biomarker of tobacco exposure. At similar smoking levels, African Americans have higher serum cotinine than Whites. UGT2B10-catalyzed cotinine glucuronidation impacts these levels, and African Americans often have low UGT2B10 activity due to a high prevalence of a
UGT2B10 splice variant (rs2942857).
METHODS: Two
UGT2B10 SNPs (rs6175900 and rs2942857) were genotyped in 289 African Americans and 627 White smokers. Each smoker was assigned a genetic score of 0, 1, or 2 based on the number of variant alleles. Total nicotine equivalents (TNE), the sum of nicotine and six metabolites, and serum cotinine and 3'-hydroxycotinine were quantified. The contribution of
UGT2B10 genetic score to cotinine concentration was determined.
RESULTS: Serum cotinine was significantly higher in smokers with
UGT2B10 genetic scores of 2 versus 0 (327 ng/mL vs. 221 ng/mL;
P < 0.001); TNEs were not different. In a linear regression model adjusted for age, gender, cigarettes per day, TNE, race, and CYP2A6 activity, geometric mean cotinine increased 43% between genetic score 2 versus 0 (
P < 0.001). A 0.1 increase in the CYP2A6 activity ratio, 3'-hydroxycotinine/cotinine, resulted in a 6% decrease in cotinine. After adjustment for
UGT2B10 genotype and the other covariants, there was no significant difference in serum cotinine by race.
CONCLUSIONS:
UGT2B10 genotype is a major contributor to cotinine levels and explains the majority of high serum cotinine in African American smokers.
IMPACT: Cotinine levels in smokers may greatly overestimate tobacco exposure and potentially misinform our understanding of ethnic/racial difference in tobacco-related disease if
UGT2B10 genotype is not taken into account.
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U2 - 10.1158/1055-9965.EPI-20-0203
DO - 10.1158/1055-9965.EPI-20-0203
M3 - Article
C2 - 32532831
AN - SCOPUS:85089125983
SN - 1055-9965
VL - 29
SP - 1673
EP - 1678
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 8
ER -
