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

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.

• Authors: 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
• Journal: Human genetics (Hum Genet) Vol. 117 Issue 1 Pg. 27-33 (Jun 2005) ISSN: 0340-6717 [Print] Germany
• PMID: 15827745 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ELAV Proteins
• Nerve Tissue Proteins
• RNA, Messenger
• RNA-Binding Proteins

Topics

• Adult
• Age of Onset
• Aged
• ELAV Proteins
• Female
• Genetic Linkage
• Haplotypes
• Humans
• Male
• Middle Aged
• Nerve Tissue Proteins (genetics)
• Parkinson Disease (genetics)
• Pedigree
• Polymorphism, Single Nucleotide
• RNA, Messenger
• RNA-Binding Proteins (genetics)