Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers

Author:

Borrego‐Soto Gissela1ORCID,Perez‐Paramo Yadira Xitlalli2ORCID,Hernández‐Cabrera Francisco3ORCID,Alvarado‐Monroy Fatima Miroslaba4,Borrego Gilberto5,Robles‐Zamora Alejandro6ORCID,Lazarus Philip2,Rojas‐Martinez Augusto7ORCID

Affiliation:

1. Department of Molecular Biosciences, School of Natural Sciences University of Texas at Austin Austin Texas USA

2. Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA

3. Department of Bioinformatics and Complex Systems, Facultad de Ciencias Físico Matemáticas Universidad Autonoma de Nuevo Leon San Nicolás de los Garza Mexico

4. National Directorate of Clinical Research, Tec Salud, Santos y de la Garza Evia Foundation Monterrey Mexico

5. Department of Computer science and design Instituto Tecnologico de Sonora Obregon Mexico

6. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud Monterrey Mexico

7. Tecnologico de Monterrey, The Institute for Obesity Research and Escuela de Medicina y Ciencias de la Salud Monterrey Mexico

Abstract

AbstractCigarette smoking remains an important health concern and is still a leading cause of preventable mortality. 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 Fagerström Test for Nicotine Dependence (FTDN) in Mexican smokers. The nicotine metabolites nicotine‐N′‐oxide, trans‐3′‐hydroxycotinine‐glucuronide (3HC‐O‐Gluc), and nicotine‐N‐Gluc (Gluc) were useful to differentiate nicotine‐dependent from non‐dependent subjects (p < .0001) with an area under the curve (AUC) of 0.7818. Genetic variants in CYP2A6, FMO3, and UGT2B7 (rs2431413, rs28363545, and rs7439326, respectively) were associated with nicotine dependence (p = .03, p = .01, p = .01, respectively). Variations in the enzymatic activity of CYP2A6 were associated with altered nicotine‐N′‐oxide and 3HC‐O‐Gluc levels. Decreased urinary levels of 3HC‐O‐Gluc and increased nicotine‐N′‐oxide 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‐O‐Gluc (p < .0001, r = .6835), while a strong negative correlation was observed with nicotine‐N′‐oxide (p < .0001, r = .6522) in nicotine‐dependent subjects. No correlations were observed in non‐nicotine‐dependent 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.

Funder

Consejo Nacional de Ciencia y Tecnología

Publisher

Wiley

Subject

General Pharmacology, Toxicology and Pharmaceutics,Neurology

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