Takeuchi Hikaru, Tomita Hiroaki, Taki Yasuyuki, Kikuchi Yoshie, Ono Chiaki, Yu Zhiqian, Sekiguchi Atsushi, Nouchi Rui, Kotozaki Yuka, Nakagawa Seishu, Miyauchi Carlos Makoto, Iizuka Kunio, Yokoyama Ryoichi, Shinada Takamitsu, Yamamoto Yuki, Hanawa Sugiko, Araki Tsuyoshi, Kunitoki Keiko, Sassa Yuko, Kawashima Ryuta
Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
Hum Brain Mapp. 2017 Jul;38(7):3516-3526. doi: 10.1002/hbm.23606. Epub 2017 Apr 12.
Vascular endothelial growth factor (VEGF) plays a critical role in the angiogenesis and proliferation of various types of cells such as neurons, astroglia, and endothelial cells in the brain. A common polymorphism in the VEGF gene (-2578 C/A) is associated with circulating VEGF levels, cancers and Alzheimer's disease. Nonetheless, the effects of this polymorphism on normal human brain volume, arterial blood volume, and blood supply remain unclear. In this study, the effects of this polymorphism on the total gray matter volume (TGMV) and total white matter volume (TWMV) using T1-weighted structural images and the total arterial blood volume (TABV) and mean cerebral blood flow (mCBF) during rest using arterial spin labeling (ASL) in 765 young adult humans were investigated. Voxel-by-voxel whole-brain analyses of these measures were also performed. Multiple regression analyses with age and sex as covariates revealed that the VEGF genotype (number of C alleles) was significantly and positively correlated with TGMV, TWMV, and TABV as well as with regional gray and white matter volumes in widespread areas and regional arterial blood volume in some areas with high arterial blood volume. However, these regional associations were not seen when the corresponding global signal was included as a covariate in the multiple regression analyses, indicating that we failed to obtain evidence of region-specific associations between these brain measures and the genotype. The results suggest that the VEGF-2578C allele, is associated with changes in the vascular system that lead to increased blood volume and larger brain volume. Hum Brain Mapp 38:3516-3526, 2017. © 2017 Wiley Periodicals, Inc.
血管内皮生长因子（VEGF）在大脑中神经元、星形胶质细胞和内皮细胞等多种类型细胞的血管生成和增殖过程中发挥着关键作用。VEGF基因中的一种常见多态性（-2578 C/A）与循环VEGF水平、癌症和阿尔茨海默病有关。尽管如此，这种多态性对正常人类脑容量、动脉血容量和血液供应的影响仍不清楚。在本研究中，我们利用T1加权结构图像研究了这种多态性对765名年轻成年人全脑灰质总体积（TGMV）和全脑白质总体积（TWMV）的影响，并利用动脉自旋标记（ASL）技术研究了静息状态下的总动脉血容量（TABV）和平均脑血流量（mCBF）。还对这些测量指标进行了逐体素全脑分析。以年龄和性别作为协变量的多元回归分析显示，VEGF基因型（C等位基因数量）与TGMV、TWMV和TABV显著正相关，也与广泛区域的局部灰质和白质体积以及一些高动脉血容量区域的局部动脉血容量显著正相关。然而，当在多元回归分析中将相应的全局信号作为协变量纳入时，未观察到这些局部关联，这表明我们未能获得这些脑测量指标与基因型之间存在区域特异性关联的证据。结果表明，VEGF - 2578C等位基因与血管系统的变化有关，这些变化导致血容量增加和脑容量增大。《人类大脑图谱》38:3516 - 3526，2017年。©2017威利期刊公司
