Drgon Tomas, Montoya Ivan, Johnson Catherine, Liu Qing-Rong, Walther Donna, Hamer Dean, Uhl George R
Molecular Neurobiology Branch, National Institutes of Health-Intramural Research Program (National Institute on Drug Abuse), Baltimore, Maryland 21224, United States of America.
Mol Med. 2009 Jan-Feb;15(1-2):21-7. doi: 10.2119/molmed.2008.00096. Epub 2008 Oct 2.
Phenotypes related to both nicotine dependence and ability to successfully quit smoking display substantial heritabilities in classical and molecular genetic studies. Twin studies suggest that some genetic components for dependence overlap with genetic components of ability to quit, but that many components do not overlap. Initial genome-wide association (GWA) studies have demonstrated haplotypes that distinguish nicotine-dependent from nondependent smokers. These haplotypes overlap partially with those that distinguish individuals who successfully quit smoking from those who were not able to quit smoking in clinical trials for smoking cessation. We now report novel genome-wide association results from National Institutes of Health research volunteers who reported smoking histories, symptoms of nicotine dependence, and ability to successfully quit smoking outside the context of a clinical trial. These results buttress data from several prior GWA studies. The data from these volunteers support the idea that previously reported studies of genes associated with smoking cessation success in clinical trial participants may also apply to smokers who are more or less able to initiate and sustain abstinence outside of clinical trial settings.
在经典遗传学和分子遗传学研究中,与尼古丁依赖及成功戒烟能力相关的表型显示出很高的遗传力。双胞胎研究表明,一些与依赖相关的遗传成分与戒烟能力的遗传成分重叠,但许多成分并不重叠。最初的全基因组关联(GWA)研究已经证实了区分尼古丁依赖吸烟者和非依赖吸烟者的单倍型。这些单倍型与在戒烟临床试验中区分成功戒烟者和未能戒烟者的单倍型部分重叠。我们现在报告来自美国国立卫生研究院研究志愿者的全新全基因组关联结果,这些志愿者报告了吸烟史、尼古丁依赖症状以及在非临床试验环境下成功戒烟的能力。这些结果支持了之前几项GWA研究的数据。这些志愿者的数据支持了这样一种观点,即先前关于临床试验参与者中与戒烟成功相关基因的研究,可能也适用于或多或少能够在临床试验环境之外开始并维持戒烟的吸烟者。