Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, People's Republic of China.
Brain Struct Funct. 2019 Nov;224(8):2619-2630. doi: 10.1007/s00429-019-01924-7. Epub 2019 Jul 22.
Catechol-O-methyltransferase (COMT) affects brain connectivity via modulating the dopamine system, with an expected greater effect of haplotypes than single-nucleotide polymorphism (SNP). The action pathway from COMT to dopamine to connectivity is theoretically dependent on the gene expression of dopamine receptors. Here, we aimed to investigate the impact of COMT haplotypes on brain functional connectivity density (FCD) in hundreds of healthy young subjects, and to disclose the association between the COMT-FCD statistical map and the spatial expression of the dopamine receptor genes. We found an inverted U-shaped modulation of COMT haplotypes on FCD in the left inferior parietal lobule that is mainly connected to the frontal and parietal cortices, with APS homozygotes exhibiting greater FCD than the other five groups. However, we failed to identify any significant effect of any SNP on FCD. Utilizing gene expression data collected from Allen human brain atlas, we found the COMT-FCD statistical map was significantly associated with the expression patterns of the dopamine receptor genes. Our results suggest that COMT haplotypes have greater impact on functional connectivity than a single genetic variation and that the association between COMT and functional connectivity may be dependent on the gene expression of dopamine receptors.
儿茶酚-O-甲基转移酶（COMT）通过调节多巴胺系统影响大脑连接，预计单核苷酸多态性（SNP）的影响比单核苷酸多态性（SNP）更大。从 COMT 到多巴胺再到连接的作用途径理论上取决于多巴胺受体的基因表达。在这里，我们旨在研究 COMT 单倍型对数百名健康年轻受试者脑功能连接密度（FCD）的影响，并揭示 COMT-FCD 统计图谱与多巴胺受体基因空间表达之间的关联。我们发现 COMT 单倍型对左侧顶下小叶 FCD 的调节呈倒 U 形，主要与额叶和顶叶皮层相连，APS 纯合子的 FCD 大于其他五组。然而，我们没有发现任何 SNP 对 FCD 有显著影响。利用从艾伦人脑图谱收集的基因表达数据，我们发现 COMT-FCD 统计图谱与多巴胺受体基因的表达模式显著相关。我们的研究结果表明，COMT 单倍型对功能连接的影响大于单一遗传变异，COMT 与功能连接之间的关联可能依赖于多巴胺受体的基因表达。
