Contents lists available at ScienceDirect Meta Gene journal homepage: www.elsevier.com/locate/mgene Association between CYP2A6 genotypes and smoking behavior in Lebanese smokers Chantal Farra a,1 , Nada Assaf a,1 , Nathalie Karaky b , Sara Diab a , Ghazi Zaatari a , Najwa Cortas a , Rose T. Daher a, ⁎ a Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon b School of Healthcare Science, Manchester Metropolitan University, Manchester, Chester Street, M1 5GD, United Kingdom ARTICLEINFO Keywords: SNP Genetic variation Genetics of smoking Nicotine metabolism Cigarette smoking Pharmacogenetics ABSTRACT Introduction: With the absence of efective reinforcement of tobacco control laws in the country, the Lebanese population has been vulnerable to the health burden of smoking. Smoking and quitting behaviors are infuenced by genetic factors, mainly CYP2A6 polymorphisms. To date, the assessment of the genetic profle and its efect on the behavior of Lebanese smokers has not yet been studied. The aim of this study was to determine the CYP2A6 polymorphisms and its relation to smoking and quitting behavior in a cohort of Lebanese smokers. Methods: Healthy adult Lebanese smokers were recruited from the American University of Beirut and its Medical Center. Their nicotine metabolite (NM) levels and CYP2A6 alleles (2, 4, 9 and 12) were determined. The smoking behavior, Nicotine Dependence Score (NDS) and quitting behavior of the participants were assessed after flling a “smoking assessment questionnaire”. Results: 53 healthy adult smokers participated in our study (M: F = 4:1, median age = 38.47 +/− 14.15 years). Mutated CYP* 2 was present in 33.9% (18/53 cases), CYP* 4 in 11.3% (6/53 cases), CYP* 9 in 100% (53/53 cases) and CYP* 12 in 86.7% (46/53 cases). Slow metabolizers constituted 90.6% of our group while 9.4% were intermediate metabolizers. Slow metabolizers smoked a smaller number of cigarettes per day (CPD) (median = 15 CPD vs 25 CPD) and had higher NM levels (median = 23 ng/mL vs 10 ng/mL or undetectable) than intermediate metabolizers. A statistically signifcant correlation with NDS and quitting behavior was not found in either group. Conclusion: In this frst study from Lebanon, a unique distribution of CYP2A6 alleles (high prevalence of CYP2A6*9 and CYP2A6*12) was detected. In accordance with previously published data, slow metabolizers smoked a lower number of CPD and had higher NM levels in their serum. Larger studies are required to fully elucidate the CYP2A6 polymorphisms of Lebanese smokers and include them in personalized smoking cessation programs. 1. Introduction Despite large scale proactive strategies deployed by governing agencies to reduce its frequency, smoking remains one of the leading causes of preventable death worldwide (Health and Services, 2014). The Lebanese population is particularly afected by this burden, with a smoking prevalence of 53.6%, a mean daily of 23 CPD, with up to 67.4% of Lebanese smokers consuming > 20 CPD (Baddoura and Wehbeh-Chidiac, 2001). Lack of implementation of an efective tobacco control law in Lebanon partly accounts for this alarming smoking epi- demic (Salti et al., 2014). Apart from environmental/social factors, genetic factors play a role in determining tobacco dependence, the number of cigarettes consumed per day and predicting smoking cessa- tion behaviors (Malaiyandi et al., 2005). Nicotine is the primary molecule responsible for the pharmacolo- gical and addictive efects of tobacco use through its action on neuronal nicotinic acetylcholine receptors (nAChRs) in the brain (Dwyer et al., 2009). The maintenance of NM levels in blood drives smoking patterns https://doi.org/10.1016/j.mgene.2019.100616 Received 23 July 2019; Received in revised form 24 September 2019; Accepted 25 September 2019 Abbreviations: CYP2A6, Cytochrome P450 2A6; CPD, Cigarette per Day; DNA, Deoxyribonucleic Acid; NM, Nicotine Metabolite; NDS, Nicotine Dependence Score; PCR, Polymerase Chain Reaction; SNP, Single Nucleotide Polymorphism ⁎ Corresponding author at: Department of Pathology & Laboratory Medicine, American University of Beirut Medical Center, P.O. Box 11-0236, Beirut, Lebanon. E-mail addresses: chantal.farra@usj.edu.lb (C. Farra), na167@aub.edu.lb (N. Assaf), smd28@mail.aub.edu (S. Diab), zaatari@aub.edu.lb (G. Zaatari), rd02@aub.edu.lb (R.T. Daher). 1 Co-primary authors. Meta Gene 23 (2020) 100616 Available online 17 October 2019 2214-5400/ © 2019 Elsevier B.V. All rights reserved. T