Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.
Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.
复制标题
烟碱乙酰胆碱受体β2亚基基因与基于系统的候选戒烟基因研究有关。
DOI：
10.1093/hmg/ddn181
复制
发表时间：
2008-09-15
影响因子：
3.5
通讯作者：
Lerman, Caryn
中科院分区：
文献类型：
--
作者：
Conti, David V.;Lee, Won;Li, Dalin;Liu, Jinghua;Van Den Berg, David;Thomas, Paul D.;Bergen, Andrew W.;Swan, Gary E.;Tyndale, Rachel F.;Benowitz, Neal L.;Lerman, Caryn
尽管药物治疗对烟草依赖的疗效已被证实，但治疗反应在不同个体之间存在很大差异。我们进行了一项基于系统的候选基因研究，研究了神经烟碱受体和多巴胺系统中58个基因中的1295个单核苷酸多态(SNPs)，以在安慰剂安慰剂随机对照临床试验中调查它们在戒烟中的作用。每个基因中的标签SNPs补充了可能的功能变异体。我们使用了主效应和处理交互作用的全局检验，调整了多个相关检验的P值。β-2烟碱型乙酰胆碱受体亚单位3‘非编码区的单核苷酸多态(Rs2072661)对治疗结束(调整后P=0.01)和6个月随访后(调整后P=0.0002)的戒断率有影响。在对测试的基因数量进行调整后，后者的P值也很显著。独立于6个月后的治疗，携带微小等位基因的个体显著降低了戒烟的几率(OR=0.31；95%CI 0.18-0.55)。估计结果表明，与携带小等位基因的个体(OR=0.83，95%CI 0.32~2.19)相比，野生型个体(OR=2.14，95%CI 1.20~3.81)的治疗效果更好，尽管这种差异仅是提示性的(P=0.10)。此外，该SNP在复发时间(P=0.0002)和在目标戒断日期(TQD)时对戒断症状的影响(P=0.0009)。总体而言，虽然我们的结果表明CHRNB2有戒烟能力的强有力证据，但这些结果需要在独立样本中复制。
Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated, there is substantial variability among individuals in treatment response. We performed a systems-based candidate gene study of 1295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled randomized clinical trial. Putative functional variants were supplemented with tagSNPs within each gene. We used global tests of main effects and treatment interactions, adjusting the P-values for multiple correlated tests. An SNP (rs2072661) in the 3′ UTR region of the β2 nicotinic acetylcholine receptor subunit (CHRNB2) has an impact on abstinence rates at the end of treatment (adjusted P = 0.01) and after a 6-month follow-up period (adjusted P = 0.0002). This latter P-value is also significant with adjustment for the number of genes tested. Independent of treatment at 6-month follow-up, individuals carrying the minor allele have substantially decreased the odds of quitting (OR = 0.31; 95% CI 0.18–0.55). Effect of estimates indicate that the treatment is more effective for individuals with the wild-type (OR = 2.14, 95% CI 1.20–3.81) compared with individuals carrying the minor allele (OR = 0.83, 95% CI 0.32–2.19), although this difference is only suggestive (P = 0.10). Furthermore, this SNP demonstrated a role in the time to relapse (P = 0.0002) and an impact on withdrawal symptoms at target quit date (TQD) (P = 0.0009). Overall, while our results indicate strong evidence for CHRNB2 in ability to quit smoking, these results require replication in an independent sample.
登录
查看更多内容
Snagger：一个用户友好的程序，用于合并用于TAGSNP选择的其他信息。
影响因子：
3
作者：
Edlund, Christopher K.;Lee, Won H.;Li, Dalin;Van Den Berg, David J.;Conti, David V.
通讯作者：
Conti, David V.
影响因子：
1.8
作者：
Conti, DV;Cortessis, V;Thomas, DC
通讯作者：
Thomas, DC
影响因子：
1.8
作者：
Cox, DG;Kraft, P
通讯作者：
Kraft, P
影响因子：
5.3
作者：
Huang, Weihua;Ma, Jennie Z.;Li, Ming D.
通讯作者：
Li, Ming D.
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ