Alpha-synuclein and familial Parkinson's disease

Nathan Pankratz, William C. Nichols, Veronika E. Elsaesser, Michael W. Pauciulo, Diane K. Marek, Cheryl A. Halter, Joanne Wojcieszek, Alice Rudolph, Ronald F. Pfeiffer, Tatiana Foroud

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Whole gene duplications and triplications of alpha-synuclein (SNCA) can cause Parkinson's disease (PD), and variation in the promoter region (Rep1) and 3′ region of SNCA has been reported to increase disease susceptibility. Within our cohort, one affected individual from each of 92 multiplex PD families showing the greatest evidence of linkage to the region around SNCA was screened for dosage alterations and sequence changes; no dosage or non-synonymous sequence changes were found. In addition, 737 individuals (from 450 multiplex PD families) that met strict diagnostic criteria for PD and did not harbor a known causative mutation, as well as 359 neurologically normal controls, were genotyped for the Rep1 polymorphism and four SNPs in the 3′ region of SNCA. The four SNPs were in high LD (r2 > 0.95) and were analyzed as a haplotype. The effects of the Rep1 genotype and the 3′ haplotype were evaluated using regression models employing only one individual per family. Cases had a 3% higher frequency of the Rep1 263 bp allele compared with controls (OR = 1.54; empirical P-value = 0.02). There was an inverse linear relationship between the number of 263 bp alleles and age of onset (empirical P-value = 0.0004). The 3′ haplotype was also associated with disease (OR = 1.29; empirical P-value = 0.01), but not age of onset (P = 0.40). These data suggest that dosage and sequence changes are a rare cause of PD, but variation in the promoter and 3′ region of SNCA convey an increased risk for PD.

Original languageEnglish
Pages (from-to)1125-1131
Number of pages7
JournalMovement Disorders
Volume24
Issue number8
DOIs
StatePublished - Jun 15 2009

Fingerprint

alpha-Synuclein
Parkinson Disease
Haplotypes
Age of Onset
Genetic Promoter Regions
Single Nucleotide Polymorphism
Alleles
Gene Duplication
Disease Susceptibility
Genotype
Mutation

Keywords

  • Alpha-synuclein
  • Association
  • Dosage
  • Parkinson's disease
  • Rep1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Pankratz, N., Nichols, W. C., Elsaesser, V. E., Pauciulo, M. W., Marek, D. K., Halter, C. A., ... Foroud, T. (2009). Alpha-synuclein and familial Parkinson's disease. Movement Disorders, 24(8), 1125-1131. https://doi.org/10.1002/mds.22524

Alpha-synuclein and familial Parkinson's disease. / Pankratz, Nathan; Nichols, William C.; Elsaesser, Veronika E.; Pauciulo, Michael W.; Marek, Diane K.; Halter, Cheryl A.; Wojcieszek, Joanne; Rudolph, Alice; Pfeiffer, Ronald F.; Foroud, Tatiana.

In: Movement Disorders, Vol. 24, No. 8, 15.06.2009, p. 1125-1131.

Research output: Contribution to journalArticle

Pankratz, N, Nichols, WC, Elsaesser, VE, Pauciulo, MW, Marek, DK, Halter, CA, Wojcieszek, J, Rudolph, A, Pfeiffer, RF & Foroud, T 2009, 'Alpha-synuclein and familial Parkinson's disease', Movement Disorders, vol. 24, no. 8, pp. 1125-1131. https://doi.org/10.1002/mds.22524
Pankratz N, Nichols WC, Elsaesser VE, Pauciulo MW, Marek DK, Halter CA et al. Alpha-synuclein and familial Parkinson's disease. Movement Disorders. 2009 Jun 15;24(8):1125-1131. https://doi.org/10.1002/mds.22524
Pankratz, Nathan ; Nichols, William C. ; Elsaesser, Veronika E. ; Pauciulo, Michael W. ; Marek, Diane K. ; Halter, Cheryl A. ; Wojcieszek, Joanne ; Rudolph, Alice ; Pfeiffer, Ronald F. ; Foroud, Tatiana. / Alpha-synuclein and familial Parkinson's disease. In: Movement Disorders. 2009 ; Vol. 24, No. 8. pp. 1125-1131.
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