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Nicotine is the substance responsible for sustained tobacco use and dependence. Identification of biomarkers underlying nicotine dependence behavior is important to identify people at risk for this dependence. In the present study, we identified biochemical and genetic biomarkers of nicotine dependence detected by the Fagerstr\u00f6m Test for Nicotine Dependence (FTDN<jats:bold>)<\/jats:bold> in Mexican smokers. The nicotine metabolites nicotine\u2010N\u2032\u2010oxide, trans\u20103\u2032\u2010hydroxycotinine\u2010glucuronide (3HC\u2010O\u2010Gluc), and nicotine\u2010N\u2010Gluc (Gluc) were useful to differentiate nicotine\u2010dependent from non\u2010dependent subjects (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) with an area under the curve (AUC) of 0.7818. Genetic variants in <jats:italic>CYP2A6<\/jats:italic>, <jats:italic>FMO3<\/jats:italic>, and <jats:italic>UGT2B7<\/jats:italic> (rs2431413, rs28363545, and rs7439326, respectively) were associated with nicotine dependence (<jats:italic>p<\/jats:italic>\u2009=\u2009.03, <jats:italic>p<\/jats:italic>\u2009=\u2009.01, <jats:italic>p<\/jats:italic>\u2009=\u2009.01, respectively). Variations in the enzymatic activity of CYP2A6 were associated with altered nicotine\u2010N\u2032\u2010oxide and 3HC\u2010O\u2010Gluc levels. Decreased urinary levels of 3HC\u2010O\u2010Gluc and increased nicotine\u2010N\u2032\u2010oxide were associated with a decrease in the functional activity of CYP2A6. A strong positive correlation was observed between the ratio of urinary 3HC\/cotinine, a measure of CYP2A6 activity, and the levels of 3HC\u2010O\u2010Gluc (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001, <jats:italic>r<\/jats:italic>\u2009=\u2009.6835), while a strong negative correlation was observed with nicotine\u2010N\u2032\u2010oxide (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001, <jats:italic>r<\/jats:italic>\u2009=\u2009.6522) in nicotine\u2010dependent subjects. No correlations were observed in non\u2010nicotine\u2010dependent subjects. These data suggest that particular urinary nicotine metabolites and genetic variants involved in nicotine metabolism are useful to identify subjects with nicotine dependence in the Mexican population.<\/jats:p>","DOI":"10.1002\/prp2.1142","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T09:21:24Z","timestamp":1696324884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5509-664X","authenticated-orcid":false,"given":"Gissela","family":"Borrego\u2010Soto","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, School of Natural Sciences University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5888-8792","authenticated-orcid":false,"given":"Yadira Xitlalli","family":"Perez\u2010Paramo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1050-2218","authenticated-orcid":false,"given":"Francisco","family":"Hern\u00e1ndez\u2010Cabrera","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Complex Systems, Facultad de Ciencias F\u00edsico Matem\u00e1ticas Universidad Autonoma de Nuevo Leon  San Nicol\u00e1s de los Garza Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Miroslaba","family":"Alvarado\u2010Monroy","sequence":"additional","affiliation":[{"name":"National Directorate of Clinical Research, Tec Salud, Santos y de la Garza Evia Foundation  Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Borrego","sequence":"additional","affiliation":[{"name":"Department of Computer science and design Instituto Tecnologico de Sonora  Obregon Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3493-8529","authenticated-orcid":false,"given":"Alejandro","family":"Robles\u2010Zamora","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud  Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Lazarus","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-6778","authenticated-orcid":false,"given":"Augusto","family":"Rojas\u2010Martinez","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, The Institute for Obesity Research and Escuela de Medicina y Ciencias de la Salud  Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Health Effects of Smoking and Tobacco Use","author":"CDCTobaccoFree","year":"2022"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","unstructured":"Genes Behavior and the Social Environment: Moving Beyond the Nature\/Nurture Debate: (719722007\u2010001).[dataset]. 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