Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported a linkage region on chromosome 1p (LOD = 3.41) for genes controlling age at onset (AAO) in Parkinson disease (PD). This region overlaps with the previously reported PARK10 locus. To identify the gene(s) associated with AAO and risk of PD in this region, we first applied a genomic convergence approach that combined gene expression and linkage data. No significant results were found. Second, we performed association mapping across a 19.2-Mb region centered under the AAO linkage peak. An iterative association mapping approach was done by initially genotyping single-nucleotide polymorphisms at an average distance of 100 kb apart and then by increasing the density of markers as needed. Using the overall data set of 267 multiplex families, we identified six associated genes in the region, but further screening of a subset of 83 families linked to the chromosome 1 locus identified only two genes significantly associated with AAO in PD: the gamma subunit of the translation initiation factor EIF2B gene (EIF2B3), which was more significant in the linked subset and the ubiquitin-specific protease 24 gene (USP24). Unexpectedly, the human immunodeficiency virus enhancer-binding protein 3 gene (HIVEP3) was found to be associated with risk for susceptibility to PD. We used several criteria to define significant results in the presence of multiple testing, including criteria derived from a novel cluster approach. The known or putative functions of these genes fit well with the current suspected pathogenic mechanisms of PD and thus show great potential as candidates for the PARK10 locus.
 ...
PMID:Identification of risk and age-at-onset genes on chromosome 1p in Parkinson disease. 1598 17

Two recent association mapping studies in Parkinson disease (PD) reported three candidate genes for the PARK10 locus: EIF2B3 as a modifier of age-at-onset of PD (min P= 0.0004) and HIVEP3 as a PD risk gene (P < or = 0.006) (Oliveira et al. 2005); and LOC200008 (CDCP2) identified by the whole genome association (WGA) study of PD of Maraganore et al. (2005). However, evaluation of the on-line PD WGA results revealed two significant SNPs in HIVEP3 in the two datasets, Tier 1 and Tier 2, used by Maraganore et al. (P < or = 0.008 for Tier 1 and P=0.03 for Tier 2 dataset). Here, we revisited both the HIVEP3 and CDCP2 loci by examining 47 SNPs, mostly tagging, in an expanded PD family dataset (293 multiplex and 467 singleton families). A discordant sibpair (DSP) dataset (one DSP per family), with similar data structure as the WGA Tier 1 dataset, was also tested. We confirmed our and other previous negative findings for CDCP2. However, five significant SNPs in HIVEP3 (min P=0.004) were observed, although the two significant HIVEP3 SNPs from the PD WGA study were not significant in our datasets. Even though the sets of significant HIVEP3 markers differ between studies, these findings strongly support HIVEP3 as a candidate for PARK10. Further testing of HIVEP3 by other groups is encouraged.
 ...
PMID:Investigation of the PARK10 gene in Parkinson disease. 1738 42