Investigation of the PARK10 gene in Parkinson disease

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.