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NEUROLOGY 2005;65:1823-1825
© 2005 American Academy of Neurology
Brief Communications

BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study

S. Karamohamed, PhD, J. C. Latourelle, MS, B. A. Racette, MD, J. S. Perlmutter, MD, G. F. Wooten, MD, M. Lew, MD, C. Klein, MD, H. Shill, MD, L. I. Golbe, MD, M. H. Mark, MD, M. Guttman, MD, G. Nicholson, PhD, J. B. Wilk, DSc, M. Saint-Hilaire, MD, A. L. DeStefano, PhD, R. Prakash, S. Tobin, J. Williamson, O. Suchowersky, MD, N. Labell, B.N.J. Growdon, MD, C. Singer, MD, R. Watts, MD, S. Goldwurm, MD, PhD, G. Pezzoli, MD, K. B. Baker, PhD, M. L. Giroux, MD, P. P. Pramstaller, MD, D. J. Burn, MD, P. Chinnery, MD, S. Sherman, MD, P. Vieregge, PhD, I. Litvan, MD, J. F. Gusella, PhD, R. H. Myers, PhD and A. Parsian, PhD

From the Department of Neurology (Drs. Karamohamed, Wilk, Saint-Hilaire, DeStefano, and Myers, J.C. Latourelle, R. Prakash, J. Williamson, and S. Tobin), Boston University School of Medicine, and Department of Biostatistics (Dr. DeStefano), Boston University School of Public Health, MA; Department of Neurology (Drs. Racette and Perlmutter), Washington University School of Medicine, Saint Louis, MO; Department of Neurology (Dr. Wooten), University of Virginia Health System, Charlottesville; Department of Neurology (Dr. Lew), University of Southern California, Los Angeles; Department of Neurology (Dr. Klein), Medical University of Lübeck, Germany; Muhammad Ali Parkinson Research Center (Dr. Shill), Barrow Neurological Institute, Phoenix, AZ; Department of Neurology (Drs. Golbe and Mark), University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick; Department of Medicine (Dr. Guttman), University of Toronto, Ontario, Canada; Neurology Department (Dr. Nicholson), University of Sydney ANZAC Research Institute, Concord Hospital, Australia; Departments of Clinical Neurosciences and Medical Genetics (Dr. Suchowersky, N. Labelle), University of Calgary, Canada; Department of Neurology (Dr. Growdon) and Molecular Neurogenetics Unit (Dr. Gusella), Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Neurology (Dr. Singer), University of Miami, FL; Department of Neurology (Dr. Watts), Emory University, Atlanta, GA; Medical Genetics Unit (Dr. Goldwurm) and Parkinson Institute (Dr. Pezzoli), Istituti Clinici di Perfezionamento, Milano, Italy; Departments of Neurology and Neuroscience (Drs. Baker and Giroux), Cleveland Clinic Foundation, OH; Department of Neurology (Dr. Pramstaller), General Regional Hospital Bolzano, Italy; Regional Neurosciences Centre (Drs. Burn and Chinnery), Newcastle General Hospital, Newcastle upon Tyne, UK; Department of Neurology (Dr. Sherman), University of Arizona, Tucson; Klinik fur Neurologie (Dr. Vieregge), Klinikum Lippe–Lemgo, Lemgo, Germany; Department of Neurology (Dr. Litvan), University of Louisville School of Medicine, KY; and Department of Pediatrics (Dr. Parsian), Human Genomics Laboratories, University of Arkansas for Medical Sciences, Little Rock.

Address correspondence and reprint requests to Dr. A. Parsian, UAMS College of Medicine, Arkansas Children’s Hospital Research Institute, 1120 Marshall St., Little Rock, AR 72202; e-mail: ParsianAbbas{at}uams.edu

Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age.

Supported by the Bumpus Foundation, PHS grant R01 NS36711-05 "Genetic Linkage Study in Parkinson’s Disease," and the Arkansas Bioscience Institute. The DNA samples contributed by the Parkinson Institute–Istituti Clinici di Perfezionamento, Milan, Italy, were from the "Human Genetic Bank of Patients Affected by Parkinson Disease and Parkinsonisms," supported by Italian Telethon grant no. GTF03009.

Disclosure: The authors report no conflicts of interest.

Received February 5, 2005. Accepted in final form August 22, 2005.




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