Journal Article

DZNE-2020-02737

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Head injury, α-synuclein Rep1, and Parkinson's disease.

Goldman, S. M. (Corresponding author) ; Kamel, F. ; Ross, G. W. ; Jewell, S. A.DZNE* ; 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
Wiley-Blackwell Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/ana.22499

Abstract: 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.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Case-Control Studies (MeSH) ; Cohort Studies (MeSH) ; Craniocerebral Trauma: blood (MeSH) ; Craniocerebral Trauma: epidemiology (MeSH) ; Craniocerebral Trauma: genetics (MeSH) ; Female (MeSH) ; Genetic Variation (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Microsatellite Repeats: genetics (MeSH) ; Middle Aged (MeSH) ; Neurodegenerative Diseases: blood (MeSH) ; Neurodegenerative Diseases: epidemiology (MeSH) ; Neurodegenerative Diseases: genetics (MeSH) ; Parkinson Disease: diagnosis (MeSH) ; Parkinson Disease: epidemiology (MeSH) ; Parkinson Disease: genetics (MeSH) ; Prospective Studies (MeSH) ; alpha-Synuclein: biosynthesis (MeSH) ; alpha-Synuclein: blood (MeSH) ; alpha-Synuclein: genetics (MeSH) ; alpha-Synuclein

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Contributing Institute(s):

1. Scientific Strategy Unit (Scientific Strategy Unit)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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