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Head injury, α-synuclein Rep1, and Parkinson's disease.
Ann Neurol. 2012 Jan; 71(1):40-8.AN

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

INTERPRETATION

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.

Authors+Show Affiliations

The Parkinson's Institute, Sunnyvale, CA 94085, USA. sgoldman@thepi.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22275250

Citation

Goldman, Samuel M., et al. "Head Injury, Α-synuclein Rep1, and Parkinson's Disease." Annals of Neurology, vol. 71, no. 1, 2012, pp. 40-8.
Goldman SM, Kamel F, Ross GW, et al. Head injury, α-synuclein Rep1, and Parkinson's disease. Ann Neurol. 2012;71(1):40-8.
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., & Tanner, C. M. (2012). Head injury, α-synuclein Rep1, and Parkinson's disease. Annals of Neurology, 71(1), 40-8. https://doi.org/10.1002/ana.22499
Goldman SM, et al. Head Injury, Α-synuclein Rep1, and Parkinson's Disease. Ann Neurol. 2012;71(1):40-8. PubMed PMID: 22275250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Head injury, α-synuclein Rep1, and Parkinson's disease. AU - Goldman,Samuel M, AU - Kamel,Freya, AU - Ross,G Webster, AU - Jewell,Sarah A, AU - Bhudhikanok,Grace S, AU - Umbach,David, AU - Marras,Connie, AU - Hauser,Robert A, AU - Jankovic,Joseph, AU - Factor,Stewart A, AU - Bressman,Susan, AU - Lyons,Kelly E, AU - Meng,Cheryl, AU - Korell,Monica, AU - Roucoux,Diana F, AU - Hoppin,Jane A, AU - Sandler,Dale P, AU - Langston,J William, AU - Tanner,Caroline M, PY - 2012/1/26/entrez PY - 2012/1/26/pubmed PY - 2012/3/10/medline SP - 40 EP - 8 JF - Annals of neurology JO - Ann Neurol VL - 71 IS - 1 N2 - OBJECTIVE: 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. METHODS: 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. RESULTS: 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). INTERPRETATION: 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. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/22275250/Head_injury_α_synuclein_Rep1_and_Parkinson's_disease_ L2 - https://doi.org/10.1002/ana.22499 DB - PRIME DP - Unbound Medicine ER -