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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Stein, Jason L. Hibar, Derrek P. De Zubicaray, Greig I. Toga, Arthur W. Jahanshad, Neda Montgomery, Grant W. Whitfield, John B. Wright, Margaret J. Martin, Nicholas G. Medland, Sarah E. Kohannim, Omid Thompson, Paul M. Mcmahon, Katie L. |
| Description | Author Affiliation: Jahanshad N ( Laboratory of NeuroImaging, Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.); |
| Abstract | Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Brain Anatomy & Histology Histocompatibility Antigens Class I Genetics Membrane Proteins Polymorphism, Genetic Transferrin Metabolism Reference Values Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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