title: The VEGF gene polymorphism impacts brain volume and arterial blood volume.
abstract: 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.
authors.affiliation: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Hikaru
authors.identifier: http://orcid.org/0000-0002-8022-9694
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.|Division of Medical Neuroimage Analysis, Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.|Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Taki
authors.affiliation: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ono
authors.affiliation: Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Division of Medical Neuroimage Analysis, Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.|Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.|Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sekiguchi
authors.affiliation: Human and Social Response Research Division, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Nouchi
authors.affiliation: Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kotozaki
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.
authors.forename: Seishu
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Arts and Sciences, Department of General Systems Studies, The University of Tokyo, Tokyo, Japan.
authors.forename: Carlos Makoto
authors.initials: CM
authors.lastname: Miyauchi
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.|Department of Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Iizuka
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.|Japan Society for the Promotion of Science, Tokyo, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Yokoyama
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Shinada
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.
authors.forename: Sugiko
authors.initials: S
authors.lastname: Hanawa
authors.affiliation: Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Araki
authors.affiliation: Faculty of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kunitoki
authors.affiliation: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sassa
authors.affiliation: Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.|Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai Japan.|Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kawashima
keywords: VEGF; blood volume; brain; brain volume; polymorphism