ABSTRACT
BACKGROUND: Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors. METHODS: One hundred and fifty patients with brain tumors completed neuropsychological tests of attention, executive functions, and memory and were genotyped for polymorphisms in the COMT, BDNF, and DTNBP1 genes. Ratings of white matter (WM) abnormalities on magnetic resonance imaging scans were performed. RESULTS: Multivariate regression shrinkage analyses, adjusted for age, education, treatment type, time since treatment completion, and tumor location, indicated a significant association between the COMT SNP rs4680 (Val158Met) and memory with lower scores in delayed recall (P < .01) among homozygotes (valine/valine). Additional COMT, BDNF and DTNBP1 SNPs were significantly associated with attention, executive functions, and memory scores. CONCLUSION: This is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.
Subject(s)
Brain Neoplasms/genetics , Brain-Derived Neurotrophic Factor/genetics , Catechol O-Methyltransferase/genetics , Cognition Disorders/genetics , Dystrophin-Associated Proteins/genetics , Adult , Aged , Aged, 80 and over , Brain Neoplasms/complications , Cognition Disorders/etiology , Dysbindin , Female , Genetic Predisposition to Disease , Genotype , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Polymorphism, Single Nucleotide , Young AdultABSTRACT
The alteration induced by diabetes on vascular permeability to serum albumin was investigated in the mesentery of streptozotocin-induced hyperglycemic rats. Double-tagged ((125)I and dinitrophenol-haptenated) heterologous albumin was intravenously administered in normal and hyperglycemic animals, and the extravasation of the tracer was evaluated by radioactivity measurements and by morphometry at the ultrastructural level using quantitative protein A-colloidal gold immunocytochemistry. The results demonstrate that diabetes induces a significant increase in the permeability of the mesentery vessels to albumin. This increase is due to a more efficient transport of macromolecules by endothelial plasmalemmal vesicles and not to leakier interendothelial junctions. Passage across the endothelial basement membranes did not appear to be restricted in either the control or diabetic condition. However, in diabetes, the mesothelial basement membrane appeared to become modified and to restrain the passage of albumin toward the peritoneal cavity. After 3 months of diabetes, the rats presented a net increase in the average diameter of the blood vessels localized in the mesentery arcada (macrovascular hyperplasy) and a notable angiogenesis, manifested at the level of the microvasculature in the mesenteric windows.
