Department of Psychiatry and Center for Nicotine and Smoking Cessation Research, Duke University, Durham, North Carolina 27705, USA.
Mol Med. 2010 Jul-Aug;16(7-8):247-53. doi: 10.2119/molmed.2009.00159. Epub 2010 Mar 17.
Improving and targeting nicotine replacement therapy (NRT) are cost-effective strategies for reducing adverse health consequences for smokers. Treatment studies document the efficacy of precessation NRT and support important roles for level of nicotine dependence and precessation smoking reduction in successful quitting. However, prior work has not identified the optimal precessation dose or means for personalizing NRT. Genome-wide association has identified groups of genomic markers associated with successful quitting, allowing us to develop a v1.0 "quit-success" genotype score. We now report influences of v1.0 quit-success genotype score, level of dependence and precessation smoking reduction in a smoking cessation trial that examined effects of 21 versus 42 mg/24 h precessation NRT. Four hundred seventy-nine smokers were randomized to 21 or 42 mg NRT, initiated 2 wks prior to target quit dates. We monitored self-reported abstinence and end-expired air carbon monoxide (CO). Genotyping used Affymetrix arrays (Santa Clara, CA, USA). The primary outcome was 10-wk continuous smoking abstinence. NRT dose, level of nicotine dependence and genotype scores displayed significant interactive effects on successful quitting. Successful abstinence also was predicted by CO reductions during precessation NRT. These results document ways in which smoking cessation strategies can be personalized based on levels of nicotine dependence, genotype scores and CO monitoring. These assessments, taken together, can help match most smokers with optimal NRT doses and help rapidly identify some who may be better treated using other methods.
改善和靶向尼古丁替代疗法(NRT)是降低吸烟者不良健康后果的具有成本效益的策略。治疗研究记录了戒烟前 NRT 的疗效,并支持尼古丁依赖程度和戒烟前吸烟量减少在成功戒烟中的重要作用。然而,先前的工作并未确定最佳的戒烟前剂量或个性化 NRT 的方法。全基因组关联已确定与成功戒烟相关的基因组标记组,使我们能够开发出 v1.0“戒烟成功”基因型评分。我们现在报告 v1.0 戒烟成功基因型评分、依赖程度和戒烟前吸烟量减少对一项戒烟试验的影响,该试验检查了 21 毫克/24 小时与 42 毫克/24 小时戒烟前 NRT 的效果。479 名吸烟者被随机分配到 21 毫克或 42 毫克 NRT 组,在目标戒烟日期前 2 周开始使用。我们监测自我报告的戒烟和呼出末一氧化碳(CO)。基因分型使用 Affymetrix 阵列(美国加利福尼亚州圣克拉拉)。主要结局是 10 周持续吸烟戒烟。NRT 剂量、尼古丁依赖程度和基因型评分对戒烟成功有显著的交互作用。戒烟前 NRT 期间 CO 减少也预测了成功戒烟。这些结果证明了可以根据尼古丁依赖程度、基因型评分和 CO 监测来个性化戒烟策略的方法。这些评估可以帮助大多数吸烟者匹配最佳的 NRT 剂量,并快速识别出一些可能需要使用其他方法治疗的人。