title: Head injury, α-synuclein Rep1, and Parkinson's disease.
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).
  
  
  CONCLUSIONS
  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.affiliation: The Parkinson's Institute, Sunnyvale, CA 94085, USA. sgoldman@thepi.org
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Goldman
authors.forename: Freya
authors.initials: F
authors.lastname: Kamel
authors.forename: G Webster
authors.initials: GW
authors.lastname: Ross
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Jewell
authors.forename: Grace S
authors.initials: GS
authors.lastname: Bhudhikanok
authors.forename: David
authors.initials: D
authors.lastname: Umbach
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Factor
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Lyons
authors.forename: Cheryl
authors.initials: C
authors.lastname: Meng
authors.forename: Monica
authors.initials: M
authors.lastname: Korell
authors.forename: Diana F
authors.initials: DF
authors.lastname: Roucoux
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hoppin
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.forename: J William
authors.initials: JW
authors.lastname: Langston
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D006259:Craniocerebral Trauma / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D010300:Parkinson Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D011446:Prospective Studies; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein