Wang Lina, Yuan Yongsheng, Wang Jianwei, Shen Yuting, Zhi Yan, Li Junyi, Wang Min, Zhang Kezhong
Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PeerJ. 2019 Nov 4;7:e7957. doi: 10.7717/peerj.7957. eCollection 2019.
We sought to explore the role of the rs393795 allelic variant in cerebral spontaneous activity and clinical features in Parkinson's disease (PD) via imaging genetic approach.
Our study recruited 50 PD and 45 healthy control (HC) participants to provide clinical, genetic, and resting state functional magnetic resonance imaging (rs-fMRI) data. All subjects were separated into 16 PD-AA, 34 PD-CA/CC, 14 HC-AA, and 31 HC-CA/CC four subgroups according to rs393795 genotyping. Afterwards, main effects and interactions of groups (PD versus HC) and genotypes (AA versus CA/CC) on cerebral function reflected by regional homogeneity (ReHo) were explored using two-way analysis of covariance (ANCOVA) after controlling age and gender. Finally, Spearman' s correlations were employed to investigate the relationships between significantly interactive brain regions and clinical manifestations in PD subgroups.
Compared with HC subjects, PD patients exhibited increased ReHo signals in left middle temporal gyrus and decreased ReHo signals in left pallidum. Compared with CA/CC carriers, AA genotype individuals showed abnormal increased ReHo signals in right inferior frontal gyrus (IFG) and supplementary motor area (SMA). Moreover, significant interactions (affected by both disease factor and allelic variation) were detected in right inferior temporal gyrus (ITG). Furthermore, aberrant increased ReHo signals in right ITG were observed in PD-AA in comparison with PD-CA/CC. Notably, ReHo values in right ITG were negatively associated with Tinetti Mobility Test (TMT) gait subscale scores and positively related to Freezing of Gait Questionnaire (FOG-Q) scores in PD-AA subgroup.
Our findings suggested that rs393795 allelic variation might have a trend to aggravate the severity of gait disorders in PD patients by altering right SMA and IFG function, and ultimately result in compensatory activation of right ITG. It could provide us with a new perspective for exploring deeply genetic mechanisms of gait disturbances in PD.
我们试图通过影像遗传学方法探讨rs393795等位基因变异在帕金森病（PD）脑自发活动及临床特征中的作用。
我们的研究招募了50名PD患者和45名健康对照（HC）参与者，以提供临床、遗传和静息态功能磁共振成像（rs-fMRI）数据。根据rs393795基因分型，将所有受试者分为16名PD-AA、34名PD-CA/CC、14名HC-AA和31名HC-CA/CC四个亚组。之后，在控制年龄和性别后，使用双向协方差分析（ANCOVA）探讨组（PD与HC）和基因型（AA与CA/CC）对由局部一致性（ReHo）反映的脑功能的主效应和交互作用。最后，采用Spearman相关性分析探讨PD亚组中显著交互作用的脑区与临床表现之间的关系。
与HC受试者相比，PD患者左侧颞中回的ReHo信号增加，左侧苍白球的ReHo信号降低。与CA/CC携带者相比，AA基因型个体右侧额下回（IFG）和辅助运动区（SMA）的ReHo信号异常增加。此外，在右侧颞下回（ITG）检测到显著的交互作用（受疾病因素和等位基因变异影响）。此外，与PD-CA/CC相比，PD-AA中右侧ITG的ReHo信号异常增加。值得注意的是，在PD-AA亚组中，右侧ITG的ReHo值与Tinetti运动测试（TMT）步态分量表评分呈负相关，与步态冻结问卷（FOG-Q）评分呈正相关。
我们的研究结果表明，rs393795等位基因变异可能通过改变右侧SMA和IFG功能，有加重PD患者步态障碍严重程度的趋势，并最终导致右侧ITG的代偿性激活。这可为深入探索PD步态障碍的遗传机制提供新的视角。
