{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:27:55Z","timestamp":1788380875339,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>\n                    Smoking continues to be the leading preventable contributor to death worldwide. Twin studies have suggested a significant genetic contribution underlying most smoking behaviors (40\u201370% heritability estimates). Candidate gene studies of smoking phenotypes have identified several pharmacogenes implicated in nicotine\u2019s pharmacokinetics (\n                    <jats:italic>CYP2A6<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2A13<\/jats:italic>\n                    ,\n                    <jats:italic>FMOs<\/jats:italic>\n                    ,\n                    <jats:italic>UGTs<\/jats:italic>\n                    , and\n                    <jats:italic>OCT2<\/jats:italic>\n                    ), and nicotine\u2019s pharmacodynamic response in the central nervous system (nicotinic acetylcholine receptors, as well as through the dopaminergic and serotonergic systems). Subsequent genome\u2010wide association studies (GWAS) have confirmed the role of certain pharmacogenes through hypothesis\u2010free approaches. Furthermore, pharmacogenes that alter the efficacy of smoking cessation pharmacotherapies, including nicotine replacement therapies, bupropion, and varenicline, may also impact quitting success. In this brief review we highlight the role of pharmacogenes in smoking behaviors, such as smoking status, consumption, nicotine dependence, spontaneous quitting, and altered abstinence to pharmacotherapies; We provide examples from initial candidate gene associations and subsequent GWAS. The genes\n                    <jats:italic>CYP2A6<\/jats:italic>\n                    and the\n                    <jats:italic>CHRNA5\u2010A3\u2010B4<\/jats:italic>\n                    confer the most replicated sources of genetic variation in smoking behaviors, likely due to their importance in nicotine\u2019s pharmacology. We will also provide examples of genetic scoring approaches, and the role of rare variants in explaining a portion of the missing heritability in smoking behaviors.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2345","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T08:48:20Z","timestamp":1624524500000},"page":"599-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Role of Pharmacogenetics in Smoking"],"prefix":"10.1111","volume":"110","author":[{"given":"Ahmed","family":"El\u2010Boraie","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto Toronto Ontario Canada"},{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel F.","family":"Tyndale","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto Toronto Ontario Canada"},{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto Ontario Canada"},{"name":"Department of Psychiatry University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2135"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0313-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/1462220031000073667"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094742"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001794"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-13665-3_3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-18-0018"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.186"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/11537850-000000000-00000"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.572"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u20100702\u2010z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14032"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.155"},{"key":"e_1_2_8_15_1","first-page":"5074","article-title":"Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco\u2010specific carcinogen, 4\u2010(methylnitrosamino)\u20101\u2010(3\u2010pyridyl)\u20101\u2010butanone","volume":"60","author":"Su T.","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.02.011"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.09.006"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3283527c1c"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12741"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000026"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntv166"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498251003713958"},{"key":"e_1_2_8_23_1","first-page":"8057","article-title":"Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco\u2010specific carcinogen NNK","volume":"63","author":"Wang H.","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.651"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000269"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070938"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2016.10.005"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.13"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1971"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.12325"},{"key":"e_1_2_8_31_1","first-page":"33","article-title":"Are serotonergic system genes associated to smoking cessation therapy success in addition to CYP2A6?","volume":"47","author":"Verde Z.","year":"2014","journal-title":"Pharmacopsychiatry"}],"container-title":["Clinical Pharmacology &amp; 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