Human Genetics

, Volume 117, Issue 1, pp 27–33

Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease

  • Maher A. Noureddine
  • Xue-Jun Qin
  • Sofia A. Oliveira
  • Tara J. Skelly
  • Joelle van der Walt
  • Michael A. Hauser
  • Margaret A. Pericak-Vance
  • Jeffery M. Vance
  • Yi-Ju Li
Original Investigation

Abstract

Inflammatory processes have been implicated in the cascade of events that lead to nerve cell death. In the nervous system, a number of genes involved in inflammation pathways are regulated post-transcriptionally via the interaction of their mRNAs with specific RNA-binding Hu proteins, the vertebrate homologues of the Drosophila ELAV (for embryonic lethal abnormal vision). The gene encoding ELAVL4, a member of the Hu family of proteins, is located 2 Mb from the chromosome 1p linkage region peak for age-at-onset (AAO) of Parkinson disease (PD) (LOD=3.41). Nine single-nucleotide polymorphisms (SNPs) in ELAVL4 were genotyped for 266 multiplex families (1,223 samples). Additional genotyping in 377 singleton families was performed for a subset of five SNPs (SNPs 1–5) that were not in linkage disequilibrium. SNP 2 (located in the first intron of ELAVL4) showed a strong significant association with AAO of PD (P=0.006), and SNP 5 (a coding SNP in ELAVL4) showed a moderately significant association (P=0.035). Haplotype analysis revealed that the A-C haplotype at SNPs 2 and 3 has the strongest significant association with AAO (P=0.0001) among all combinations of two or three loci. The A-C haplotype remained significant for AAO after the inclusion of the C allele at SNP 5 to this haplotype (A-C-C haplotype, P=0.00018). Although SNP 5 was found to associate with PD risk in the early-onset subset of PD families (at least one affected with AAO <40 years, 60 families), we believe that it is a by-product of its association with AAO. Taken together, these results suggest a potential role for ELAVL4 as a modifier gene for AAO of PD.

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Maher A. Noureddine
    • 1
  • Xue-Jun Qin
    • 1
  • Sofia A. Oliveira
    • 1
  • Tara J. Skelly
    • 1
  • Joelle van der Walt
    • 1
  • Michael A. Hauser
    • 1
  • Margaret A. Pericak-Vance
    • 1
  • Jeffery M. Vance
    • 1
  • Yi-Ju Li
    • 1
  1. 1.Department of Medicine and Center for Human GeneticsDuke University Medical CenterDurhamUSA

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