Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups

摘要: Nicotine metabolism influences smoking behavior and differences in probably contribute to ethnic variability lung cancer risk. We report here on the proportion of nicotine by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation flavin monooxygenase 3-catalyzed N-oxidation five ethnic/racial groups role UGT2B10 genotype metabolic patterns observed. its metabolites were quantified urine from African American (AA, n = 364), Native Hawaiian (NH, 311), White (n 437), Latino (LA, 453) Japanese (JA, 674) smokers. Total equivalents, sum six metabolites, phenotypes calculated. The relationship pathways was determined for each group; geometric means computed adjusted age, sex, creatinine, body mass index. unique across groups, C-oxidation lowest JA NH (P < 0.0001), AA 0.0001). There no difference among Whites LA. cotinine glucuronide ratios 2- 3-fold lower compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) splice variant (rs116294140) accounted 33% variation glucuronidation. In AA, majority reduced allele carriers had increased levels 0.0099). Our data indicate that relative importance varies ethnicity, all should be considered when characterizing