부산대학교 도서관

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 theDrosophilaELAV (forembryoniclethalabnormalvision). 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) inELAVL4were 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 ofELAVL4) showed a strong significant association with AAO of PD (P=0.006), and SNP 5 (a coding SNP inELAVL4) showed a moderately significant association (P=0.035). Haplotype analysis revealed that theA-Chaplotype at SNPs 2 and 3 has the strongest significant association with AAO (P=0.0001) among all combinations of two or three loci. TheA-Chaplotype remained significant for AAO after the inclusion of the C allele at SNP 5 to this haplotype (A-C-Chaplotype,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 forELAVL4as a modifier gene for AAO of PD. [ABSTRACT FROM AUTHOR]