Head injury, alpha-synuclein Rep1, and Parkinson's disease
Version of Record online: 24 JAN 2012
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 71, Issue 1, pages 40–48, January 2012
How to Cite
Goldman, S. M., Kamel, F., Ross, G. W., Jewell, S. A., Bhudhikanok, G. S., Umbach, D., Marras, C., Hauser, R. A., Jankovic, J., Factor, S. A., Bressman, S., Lyons, K. E., Meng, C., Korell, M., Roucoux, D. F., Hoppin, J. A., Sandler, D. P., Langston, J. W. and Tanner, C. M. (2012), Head injury, alpha-synuclein Rep1, and Parkinson's disease. Ann Neurol., 71: 40–48. doi: 10.1002/ana.22499
- Issue online: 24 JAN 2012
- Version of Record online: 24 JAN 2012
- Accepted manuscript online: 2 JUN 2011 07:34AM EST
- Manuscript Accepted: 27 MAY 2011
- Manuscript Received: 15 NOV 2010
- Manuscript Revised: 19 MAY 2010
- Intramural Research Program of the NIH
- National Institute of Environmental Health Sciences [NIEHS]. Grant Numbers: Z01-ES044007, Z01-ES049030, R01-ES10803, U54 ES012077, NCI Z01-CP010119)
- Michael J. Fox Foundation
- Parkinson's Unity Walk
- Parkinson's Institute
To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α-synuclein, modifies the association between head injury and Parkinson's disease (PD) risk.
Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), 2 independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury.
Consistent with prior reports, relative to medium-length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5–0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95–2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9–1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5–19; SEARCH OR, 2.3; 95% CI, 0.6–9.2; pooled OR, 3.5; 95% CI 1.4–9.2, p-interaction = 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p = 0.03).
While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential. ANN NEUROL 2012;71:40–48