Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
PLoS One. 2013 Oct 16;8(10):e78697. doi: 10.1371/journal.pone.0078697. eCollection 2013.
The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype × gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial superior frontal gyrus (mSFG) was found only in male Val/Val subjects. The rsFC analysis revealed that both the PCC and mSFG were functionally correlated with brain regions of the default mode network (DMN). Both of these regions showed decreased rsFCs with different parts of the frontopolar cortex of the DMN in Val/Val individuals than Met carriers. Our findings suggest that the COMT Val158Met polymorphism modulates both the structure and functional connectivity within the DMN and that gender interactions should be considered in studies of the effect of this genetic variant, especially those involving prefrontal morphology.
儿茶酚-O-甲基转移酶（COMT）Val158Met 多态性对大脑结构和功能的影响之前已经分别进行了区域性研究；这使得我们无法全面了解该基因变异的影响。此外，不能忽视性别差异，因为雌激素对 COMT 活性有干扰作用。我们检查了 323 名年轻健康的中国汉族受试者，以体素为单位分析了整个大脑中 Val/Val 个体与 Met 携带者之间的灰质体积（GMV）差异。我们对基因型效应和基因型与性别相互作用感兴趣。然后，我们将这些具有 GMV 差异的脑区作为种子，计算与大脑其他部位的静息状态功能连接（rsFC）；我们还测试了 rsFC 中的基因型差异和性别相互作用。与 Met 携带者相比，Val/Val 个体的后扣带回皮层（PCC）GMV 减少；仅在男性 Val/Val 受试者中发现内侧额上回（mSFG）GMV 减少。rsFC 分析表明，PCC 和 mSFG 都与默认模式网络（DMN）的大脑区域有功能相关性。与 Met 携带者相比，这两个区域的 rsFC 都显示出 Val/Val 个体与 DMN 的额极前部的不同部分的连接减少。我们的研究结果表明，COMT Val158Met 多态性调节 DMN 内的结构和功能连接，在研究该遗传变异的影响时应考虑性别相互作用，尤其是涉及前额叶形态的研究。
