title: Australian data and meta-analysis lend support for alpha-synuclein (NACP-Rep1) as a risk factor for Parkinson's disease.
abstract: It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic Parkinson's disease (PD). The polymorphic mixed sequence repeat (NACP-Rep1) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for PD with conflicting results. We report genotype and allele distributions at this locus from 369 PD cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association.
authors.affiliation: Department of Neurology, School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia. gmellick@soms.uq.edu.au
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.forename: Demetrius M
authors.initials: DM
authors.lastname: Maraganore
authors.forename: Peter A
authors.initials: PA
authors.lastname: Silburn
mesh_terms: D000368:Aged; D001315:Australia; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein