title: Association analysis of PARP1 polymorphisms with Parkinson's disease.
abstract: Alpha-synuclein accumulation in intracellular inclusions, oxidative stress and microglia-mediated inflammation in the substantia nigra are crucial events in the pathogenesis of Parkinson's disease (PD). Poly (ADP-ribose) polymerase-1 (PARP1), a DNA-binding enzyme and transcriptional regulator, plays an important role in modulating the cellular response to oxidative stress, inflammatory stimuli, and in apoptotic cell death. Inhibition of PARP1 results in significant neuroprotection in PD animal models; moreover PARP1 has a physiological role in the regulation of alpha-synuclein expression. A previous study had demonstrated that variants located within the PARP1 gene promoter reduce the risk of PD and delay the disease age at onset. In light of these data, we carried out an association study to investigate whether variability within this gene is associated with PD risk and disease age at onset in an Italian cohort composed of 600 PD patients and 592 healthy controls. To this purpose, we used a comprehensive tag SNP approach spanning the entire gene and the upstream and downstream regions. We did not detect any significant association of the PARP1 gene with PD either at genotypic or haplotypic level; none of the 11 genotyped SNPs was significantly associated with PD age at onset. We conclude that, despite previous evidence, PARP1 is not a susceptibility gene for PD in our population.
authors.affiliation: Department of Neurology, San Gerardo Hospital, Monza, Italy. brighinalaura@hotmail.com
authors.forename: Laura
authors.initials: L
authors.lastname: Brighina
authors.forename: Chiara
authors.initials: C
authors.lastname: Riva
authors.forename: Francesca
authors.initials: F
authors.lastname: Bertola
authors.forename: Silvia
authors.initials: S
authors.lastname: Fermi
authors.forename: Enrico
authors.initials: E
authors.lastname: Saracchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Piolti
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrarese
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*
chemical_list: C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases