Gene-Gene Interactions Among CHRNA4, CHRNB2, BDNF, and NTRK2 in Nicotine Dependence
Gene-Gene Interactions Among CHRNA4, CHRNB2, BDNF, and NTRK2 in Nicotine Dependence
复制标题
DOI：
10.1016/j.biopsych.2008.04.026
复制
发表时间：
2008-12-01
影响因子：
10.6
通讯作者：
Elston, Robert C.
中科院分区：
文献类型：
--
作者：
Li, Ming D.;Lou, Xiang-Yang;Elston, Robert C.
背景：流行病学数据表明尼古丁依赖受基因、环境因素及其相互作用的影响。尽管分子实验证明脑源性神经营养因子(BDNF)通过神经营养酪氨酸激酶受体2(NTRK2)发挥作用，并且α4(CHRNA4)和β2(CHRNB2)亚基都需要形成功能性的含α4β2的尼古丁受体(NAChRs)，但尚未有研究证明这四个基因之间存在基因-基因相互作用。方法：为了确定这四个基因之间是否存在基因-基因相互作用，我们对CHRNA4和BDNF的6个单核苷酸多态(SNPs)和NTRK2的9个SNP进行了基因分型。结果：利用我们最近开发的广义多因素降维算法，我们发现CHRNA4与CHRNB2、CHRNA4与NTRK2、CHRNB2与NTRK2、BDNF与NTRK2基因对之间存在着极显著的基因-基因交互作用(p
Background: Epidemiological data indicate that nicotine dependence (ND) are influenced by genes, environmental factors, and their interactions. Although it has been documented from molecular experiments that brain-derived neurotrophic factor (BDNF) exerts its functions via neurotrophic tyrosine kinase receptor 2 (NTRK2) and both alpha 4 (CHRNA4) and beta 2 (CHRNB2) subunits are required to form functional alpha 4 beta 2-containing nicotinic receptors (nAChRs), no study is reported demonstrating that there exist gene-gene interactions among the four genes in affecting ND.Methods: To determine if gene-gene interactions exist among the four genes, we genotyped six single nucleotide polymorphisms (SNPs) for CHRNA4 and BDNF, nine SNPs for NTRK2, and four SNPs for CHRNB2 in a case-control sample containing 275 unrelated smokers with a Fagerstrom Test for Nicotine Dependence score of 4.0 or more and 348 unrelated nonsmokers.Results: By using a generalized multifactor dimensionality reduction algorithm recently developed by us, we found highly significant gene-gene interactions for the gene pairs of CHRNA4 and CHRNB2, CHRNA4 and NTRK2, CHRNB2 and NTRK2, and BDNF and NTRK2 (p