title: 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.affiliation: Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Maher A
authors.initials: MA
authors.lastname: Noureddine
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Qin
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
authors.forename: Tara J
authors.initials: TJ
authors.lastname: Skelly
authors.forename: Joelle
authors.initials: J
authors.lastname: van der Walt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D051959:ELAV Proteins; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D051959:ELAV Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins