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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.

SUBMITTER: Takeuchi H

PROVIDER: S-EPMC6866916 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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The VEGF gene polymorphism impacts brain volume and arterial blood volume.

Takeuchi Hikaru H Tomita Hiroaki H Taki Yasuyuki Y Kikuchi Yoshie Y Ono Chiaki C Yu Zhiqian Z Sekiguchi Atsushi A Nouchi Rui R Kotozaki Yuka Y Nakagawa Seishu S Miyauchi Carlos Makoto CM Iizuka Kunio K Yokoyama Ryoichi R Shinada Takamitsu T Yamamoto Yuki Y Hanawa Sugiko S Araki Tsuyoshi T Kunitoki Keiko K Sassa Yuko Y Kawashima Ryuta R

Human brain mapping 20170412 7

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 ...[more]

PMID: 28402004

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Project description:BackgroundChildhood trauma is one of the most extensively studied and well-supported environmental risk factors for the development of mental health problems. The human tryptophan hydroxylase 2 (TPH2) gene is one of the most promising candidate genes in numerous psychiatric disorders. However, it is now widely acknowledged that neither genetic variation nor environmental exposure alone can fully explain all the phenotypic variance observed in psychiatric disorders. Therefore, it is necessary to consider the interaction between the two factors in psychiatric research.MethodsWe enrolled a sizable nonclinical cohort of 786 young, healthy adults who underwent structural MRI scans and completed genotyping, the Childhood Trauma Questionnaire (CTQ) and behavioural scores. We identified the interaction between childhood trauma and the TPH2 rs7305115 gene polymorphism in the gray matter volume (GMV) of specific brain subregions and the behaviour in our sample using a multiple linear regression framework. We utilized mediation effect analysis to identify environment /gene-brain-behaviour relationships.ResultsWe found that childhood trauma and TPH2 rs7305115 interacted in both behaviour and the GMV of brain subregions. Our findings indicated that the GMV of the right posterior parietal thalamus served as a significant mediator supporting relationship between childhood trauma (measured by CTQ score) and anxiety scores in our study population, and the process was partly modulated by the TPH2 rs7305115 gene polymorphism. Moreover, we found only a main effect of childhood trauma in the GMV of the right parahippocampal gyrus area, supporting the relationship between childhood trauma and anxiety scores as a significant mediator.ConclusionsOur findings suggest that early-life trauma may have a specific and long-term structural effect on brain GMV, potentially leading to altered cognitive and emotional processes involving the parahippocampal gyrus and thalamus that may also be modulated by the TPH2 gene polymorphism. This finding highlights the importance of considering genetic factors when examining the impact of early-life experiences on brain structure and function. Gene‒environment studies can be regarded as a powerful objective supplement for targeted therapy, early diagnosis and treatment evaluation in the future.

Project description:BackgroundThe VEGF gene polymorphism rs699947 related to clinical pathology, mortality, and recurrence of HCC. Few studies mentioned an association between VEGF gene polymorphisms with illness progression in chronic liver disease. We aimed to explore differences of VEGF gene polymorphism rs699947 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma patients in Indonesian population.MethodsA cross-sectional study with consecutive sampling and without matching was performed during a 3 years period (2011-2014) at Dr. Sardjito General Hospital Yogyakarta, Indonesia. Blood DNA was sequenced from 123 subjects with chronic liver diseases [39 chronic hepatitis (CH), 39 liver cirrhosis (LC), and 45 hepatocellular carcinoma (HCC)]. 59 healthy subjects also participated. Using isolated VEGF genes for specific primers for rs699947, blood samples were examined by targeting DNA sequences with Applied Bio systems. All data were analyzed using STATA version 11.0 with significance level at P<0.05.ResultsThe mean of age in HCC and LC subjects were older than in CH and healthy (P value <0.05); there were more males in LC, HCC and the healthy groups but not in CH (P>0.05). HBV was the dominant etiology in HCC, LC, and CH besides HCV and non HBV-HCV (P<0.05). There were significant differences in the SNP -2578 distributions of allele C compared to allele A in all subjects (healthy vs. LC, and HCC; LC vs. CH (P<0.05), but no significant difference A>C vs. C>C, and genotypes distribution. Proportion of SNP -2578 A>C vs. C>C CH 1.8:1; HCC 1.4:1; healthy 1.7:1; but its proportion in LC was inversed (1:1.2). Genotype A was low in all subjects (5%-11%). Significant difference of allele distribution was found in healthy vs. LC, and HCC; CH vs. LC. Based on HWE analyses, distribution of allele C was dominant. There were not significant differences in deletion, insertion-deletion at -2547 until -2526, and haplotype (Ht) CCGACCCC (P>0.05). The OR analyses of allele and SNP showed that allele A can be a predictor of disease progression in LC to HCC (OR 2.26) and healthy to LC (OR 1.65); and SNP A>C also can be a predictor in healthy to HCC (OR 1.41) and CH (OR 1.14).ConclusionThe occurrence of allele A and SNP A>C VEGF gene (-2578) might predict illness progression from healthy to CH, LC or HCC and LC to HCC.

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The VEGF gene polymorphism impacts brain volume and arterial blood volume.

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The VEGF gene polymorphism impacts brain volume and arterial blood volume.

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