INTEGRATING GENETICS, ADVERSE EVENTS, AND ADHERENCE TO IMPROVE SMOKING CESSATION

 描述(由申请人提供)：在使用药物辅助戒烟时，不良事件很常见(Piper等人)。2009年)。根据患者的遗传特征分配最佳戒烟药物的可能性正在迅速成为现实：与尼古丁依赖和新陈代谢相关的基因变异已被证明对戒烟药物治疗的效用有影响(Chen等人)。2012年，卑尔根等人。2013年，法尔科内等人。2011年)，有初步数据支持这一观点，即这些变体也与戒烟药物治疗的不良事件有关(King等人。2012年)。该项目的目标是评估基因变异在使用尼古丁替代疗法或安非他酮帮助吸烟者戒烟时预测不良事件的效用。为了实现这一目标，我们将使用威斯康星大学跨学科烟草使用研究中心研究(UW-TTURC)的不良事件、依从性、戒烟结果和基因数据。具体目的是(1)在UW-TTURC研究中确定基因变异与可归因于戒烟药物的不良事件之间的联系，重点关注以前与尼古丁依赖相关的基因(例如尼古丁受体亚单位基因CHRNA5和尼古丁代谢基因CYP2A6)或安非他酮代谢(例如CYP2B6)，以及(2)确定不良事件和坚持治疗在多大程度上介导了基因变异和成功戒烟之间的联系。这项研究的结果应该会提高我们预测使用特定戒烟药物时谁会经历不良事件的能力。这些知识将导致个性化的戒烟疗法，从而减少不良事件，提高依从性，并最终增加戒烟成功率。

 DESCRIPTION (provided by applicant): Adverse events are common while using medications to assist an attempt to quit smoking (Piper et al. 2009). The possibility of assigning optimal smoking cessation medications based on a patient's genetic profile is rapidly becoming a reality: genetic variants associated with nicotine dependence and metabolism have been demonstrated to have an impact on utility of smoking cessation pharmacotherapy (Chen et al. 2012, Bergen et al. 2013, Falcone et al. 2011) and there is preliminary data to support the idea that these variants are also associated with adverse events attributable to smoking cessation pharmacotherapy (King et al. 2012). The goal of this project is to evaluate the utility of genetic variants to predict adverse events while using nicotine replacement therapy or bupropion to help a smoker to quit. To achieve this goal, we will use adverse event, adherence, cessation outcome, and genotype data from the University of Wisconsin Transdisciplinary Tobacco Use Research Center study (UW-TTURC). The specific aims are (1) to determine associations between genetic variants and adverse events attributable to smoking cessation medications in the UW-TTURC study, focusing on genes previously associated with nicotine dependence (e.g. nicotinic receptor subunit genes CHRNA5 and nicotine metabolism gene CYP2A6), or bupropion metabolism (e.g. CYP2B6), and (2) to determine the extent to which associations between genetic variants and successful smoking cessation are mediated by adverse events and adherence. Results from this study should improve our ability to predict who will experience adverse events due when using particular smoking cessation medications. This knowledge will lead to personalized smoking cessation therapies that will decrease adverse events, improve adherence, and ultimately increase smoking cessation success.