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Human Molecular Genetics Advance Access published online on July 26, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm189
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Preservation of Gray Matter Volume in Multiple Sclerosis Patients with the Met Allele of the rs6265 (Val66Met) SNP of Brain Derived Neurotrophic Factor (BDNF)

Robert Zivadinov1,2, Bianca Weinstock-Guttman2, Ralph Benedict2, Miriam Tamaño-Blanco3, Sara Hussein1, Nadir Abdelrahman1, Jackie Durfee1 and Murali Ramanathan2,3,*

1 Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY 14203 2 Jacobs Neurological Institute, Buffalo General Hospital, Buffalo, NY 14203 3 Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY 14260-1200

* CORRESPONDENCE: Murali Ramanathan 427 Cooke Hall, Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY 14260, (716) 645-2842 ext. 242. FAX 716-645-3693. E-mail murali{at}buffalo.edu

Received June 12, 2007; Revised July 9, 2007; Accepted July 12, 2007

Objectives: To investigate the association of the rs6265 (Val66Met) single nucleotide polymorphism (SNP) of brain derived neurotrophic factor (BDNF) with brain morphometry and functional status as measured by quantitative magnetic resonance imaging (MRI) and neurocognitive testing in multiple sclerosis (MS) patients.

Background: BDNF is released by neurons and by immune cells in MS brain. The rs6265 SNP variation of BDNF causes substitution of valine (Val) for methionine (Met) and interferes with activity-dependent BDNF secretion.

Methods: A total of 209 treated MS patients (161 females; 48 males) underwent clinical brain MRI and were genotyped for the BDNF rs6265 Val66Met SNP. A subset of 108 patients had neurocognitive testing for processing speed, memory and executive function. The MRI measurements included T2- and T1-lesion volume (LV); normalized brain volume measures of whole brain volume (NBV), white and gray matter volume (NWMV and NGMV); and the diffusion weighted imaging measure of whole brain parenchyma diffusivity (MPD).

Results: The Met66 allele status was positively associated with NGMV (p = 0.015, standardized b = 0.15) and negatively associated with T2-LV (p = 0.041, standardized b = -0.14). There were no significant associations between Met66 allele status and T1-LV, NWMV or MPD. On the Paced Serial Addition Test (PASAT), a trend (p = 0.057) favoring the Met66 allele group was observed. There were no significant associations between Met66 allele status and other neurocognitive measures.

Conclusions: The BDNF Met66 allele is associated with lower damage as evidenced by measurement of NGMV and T2-LV in MS patients.


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