Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor

• Published in: Human molecular genetics 2007-11, Vol.16 (22), p.2659-2668
• Main Authors: Zivadinov, Robert, Weinstock-Guttman, Bianca, Benedict, Ralph, Tamaño-Blanco, Miriam, Hussein, Sara, Abdelrahman, Nadir, Durfee, Jackie, Ramanathan, Murali
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Brain - pathology; Brain-Derived Neurotrophic Factor - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Methionine - genetics; Middle Aged; Molecular and cellular biology; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Neuropsychological Tests; Polymorphism, Single Nucleotide
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddm189

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. 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. 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 (WB) volume, white and gray matter volume (NWMV and NGMV) and the diffusion-weighted imaging measure of WB mean parenchyma diffusivity (MPD). The Met66 allele status was positively associated with NGMV (P = 0.015, standardized β = 0.15) and negatively associated with T2-LV (P = 0.041, standardized β = −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. The BDNF Met66 allele is associated with lower damage as evidenced by measurement of NGMV and T2-LV in MS patients.