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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Noureddine, MA; Qin, X-J; Oliveira, SA; Skelly, TJ; van der Walt, J; Hauser, MA; Pericak-Vance, MA; Vance, JM; Li, Y-J

Published Date

  • June 2005

Published In

Volume / Issue

  • 117 / 1

Start / End Page

  • 27 - 33

PubMed ID

  • 15827745

International Standard Serial Number (ISSN)

  • 0340-6717

Digital Object Identifier (DOI)

  • 10.1007/s00439-005-1259-2


  • eng

Conference Location

  • Germany