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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalHuman Genetics
Volume117
Issue number1
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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RNA-Binding Proteins
Single Nucleotide Polymorphism
Parkinson Disease
Neurons
Haplotypes
Age of Onset
Modifier Genes
Chromosomes, Human, Pair 2
Linkage Disequilibrium
Introns
Nervous System
Genes
Drosophila
Vertebrates
Cell Death
Alleles
Inflammation
Messenger RNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Noureddine, M. A., Qin, X. J., Oliveira, S. A., Skelly, T. J., van der Walt, J., Hauser, M. A., ... Li, Y. J. (2005). Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. Human Genetics, 117(1), 27-33. https://doi.org/10.1007/s00439-005-1259-2

Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. / Noureddine, Maher A.; Qin, Xue Jun; Oliveira, Sofia A.; Skelly, Tara J.; van der Walt, Joelle; Hauser, Michael A.; Pericak-Vance, Margaret A; Vance, Jeffery M; Li, Yi Ju.

In: Human Genetics, Vol. 117, No. 1, 01.06.2005, p. 27-33.

Research output: Contribution to journalArticle

Noureddine, MA, Qin, XJ, Oliveira, SA, Skelly, TJ, van der Walt, J, Hauser, MA, Pericak-Vance, MA, Vance, JM & Li, YJ 2005, 'Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease', Human Genetics, vol. 117, no. 1, pp. 27-33. https://doi.org/10.1007/s00439-005-1259-2
Noureddine MA, Qin XJ, Oliveira SA, Skelly TJ, van der Walt J, Hauser MA et al. Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. Human Genetics. 2005 Jun 1;117(1):27-33. https://doi.org/10.1007/s00439-005-1259-2
Noureddine, Maher A. ; Qin, Xue Jun ; Oliveira, Sofia A. ; Skelly, Tara J. ; van der Walt, Joelle ; Hauser, Michael A. ; Pericak-Vance, Margaret A ; Vance, Jeffery M ; Li, Yi Ju. / Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. In: Human Genetics. 2005 ; Vol. 117, No. 1. pp. 27-33.
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AU - van der Walt, Joelle

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