Shen Zhujing, Huang Peiyu, Wang Chao, Qian Wei, Luo Xiao, Gu Quanquan, Chen Huan, Wang Hongjuan, Yang Yihong, Zhang Minming
Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
China National Tobacco Quality Supervision & Test Center, Zhengzhou, China.
Eur J Neurosci. 2019 Aug;50(3):2201-2210. doi: 10.1111/ejn.14282. Epub 2018 Dec 11.
The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, serotonin and norepinephrine, and its genetic polymorphism (rs1137070) influences its activity level and is associated with smoking behaviors. However, the underlying neural mechanisms of the gene × environment interactions remain largely unknown. In this study, we aimed to explore the interactive effects of the rs1137070 and cigarette smoking on gray matter volume (GMV) and functional connectivity strength (FCS). A total of 81 smokers and 42 nonsmokers were enrolled in the present study. Voxel-based morphometry analysis showed a significant rs1137070 genotype × smoking effect on the GMV of the left orbitofrontal cortex (OFC), such that individuals with risk allele had greater GMV among nonsmokers but not smokers. Meanwhile, rs1137070 variant and nicotine dependence interactively altered the FCS of the right hippocampus, the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex and bilateral OFC. In addition, the FCS in the left IPL was correlated with smoking initiation and smoking years in smokers with the risk allele. These findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression.
单胺氧化酶A（MAOA）可代谢多巴胺、5-羟色胺和去甲肾上腺素等单胺类神经递质，其基因多态性（rs1137070）会影响其活性水平，并与吸烟行为相关。然而，基因×环境相互作用的潜在神经机制仍 largely unknown。在本研究中，我们旨在探究rs1137070与吸烟对灰质体积（GMV）和功能连接强度（FCS）的交互作用。本研究共纳入了81名吸烟者和42名非吸烟者。基于体素的形态学分析显示，rs1137070基因型×吸烟对左侧眶额皮质（OFC）的GMV有显著影响，即具有风险等位基因的个体在非吸烟者中GMV更大，但在吸烟者中并非如此。同时，rs1137070变异与尼古丁依赖交互改变了右侧海马体、左侧顶下小叶（IPL）、左侧背外侧前额叶皮质和双侧OFC的FCS。此外，在具有风险等位基因的吸烟者中，左侧IPL的FCS与开始吸烟的时间和吸烟年限相关。这些发现表明，MAOA rs1137070通过影响与奖赏和注意力相关的脑回路，导致对尼古丁依赖的易感性，并在疾病进展过程中与吸烟相互作用。
