Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity
Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity
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DOI：
10.1007/s00439-010-0876-6
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发表时间：
2010-11-01
期刊：
影响因子：
5.3
通讯作者：
Boscarino, Joseph A.
中科院分区：
文献类型：
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作者：
Erlich, Porat M.;Hoffman, Stuart N.;Boscarino, Joseph A.
染色体15q25.1上的一个基因座此前与尼古丁、酒精和可卡因依赖、吸烟和肺癌有关，该基因座编码在中边缘系统中表达的尼古丁乙酰胆碱受体（nAChR）亚基，并被认为介导物质依赖。阿片类药物依赖的严重程度（ODS），尼古丁依赖的严重程度（NDS），吸烟状态和数量，以及尝试戒烟的次数进行了评估，使用问卷调查工具在505例受试者谁是处方阿片类药物治疗慢性疼痛门诊实践网站。多变量回归用于测试这些表型与染色体15q25.1上的nAChR基因簇中的5个SNP的遗传关联，调整背景变量。CHRNA5中的编码变体（rs16969968[A]）与1.4单位的高ODS显著相关（p < 0.00017）。CHRNA3的3'非翻译区的一个变异体（rs660652[G]）与终生吸烟的几率增加1.7倍（p < 0.0092）、NDS增加1.1个单位（p < 0.0007）、吸烟包年增加0.7包年（p < 0.0038）和终生尝试戒烟增加0.8包年（p < 0.0084）显著相关。我们的数据表明，染色体15q25.1上的nAChR基因簇中的DNA变异与ODS以及NDS和相关吸烟表型相关。虽然该位点与NDS和吸烟表型的关联是众所周知的，但与ODS（阿片类物质依赖的一个维度）的关联是新颖的，需要在独立研究中进行验证。
A locus on chromosome 15q25.1 previously implicated in nicotine, alcohol, and cocaine dependence, smoking, and lung cancer encodes subunits of the nicotinic acetylcholine receptor (nAChR) expressed in the mesolimbic system and thought to mediate substance dependence. Opioid dependence severity (ODS), nicotine dependence severity (NDS), smoking status and quantity, and the number of attempts to quit were assessed using questionnaire instruments in 505 subjects who were prescribed opioid medications for chronic pain in outpatient practice sites. Multivariate regression was used to test for genetic association of these phenotypes with 5 SNPs in the nAChR gene cluster on chromosome 15q25.1, adjusting for background variables. A coding variant in CHRNA5 (rs16969968[A]) was significantly associated with 1.4-unit higher ODS (p < 0.00017). A variant in the 3' untranslated region of CHRNA3 (rs660652[G]) was significantly associated with 1.7-fold higher odds of lifetime smoking (p < 0.0092), 1.1-unit higher NDS (p < 0.0007), 0.7 more pack-years of cigarette smoking (p < 0.0038), and 0.8 more lifetime attempts to quit (p < 0.0084). Our data suggest an association of DNA variants in the nAChR gene cluster on chromosome 15q25.1 with ODS, as well as NDS and related smoking phenotypes. While the association of this locus with NDS and smoking phenotypes is well known, the association with ODS, a dimension of opioid substance dependence, is novel and requires verification in independent studies.