title: SNCA and MAPT genes: Independent and joint effects in Parkinson disease in the Italian population.
abstract: BACKGROUND
  Significant efforts have been focused on investigating the contribution of common variants to Parkinson disease (PD) risk. Several independent GWAS and metanalysis studies have shown a genome-wide significant association of single nucleotide polymorphisms (SNPs) in the α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) regions. Here we investigated the role of SNCA and MAPT as PD susceptibility genes in a large Italian population of 904 patients and 891 controls. An evaluation of gene-gene and gene-environment interactions in association with PD was also attempted.
  
  
  METHODS
  The SNCA Rep1 microsatellite was genotyped by a fluorescent PCR assay, whereas the SNPlex genotyping system was used to genotype 12 additional markers across the SNCA gene, and 2 SNPs tagging the risk MAPT H1 haplotype.
  
  
  RESULTS
  Single-marker analysis demonstrated nominal evidence of association for: i) the 261-bp-long allele of Rep1; ii) 7 SNPs in the SNCA region (top SNP: rs356186, P = 3.08 × 10(-04), intron 4); iii) both SNPs identifying the MAPT H1 haplotype (P = 4.63 × 10(-04) and P = 4.23 × 10(-04) for rs1800547 and rs9468, respectively). Moreover, we found a highly significant protective haplotype spanning ∼83 kb from intron 4 to the 3' end of SNCA (P = 1.29 × 10(-05)).
  
  
  CONCLUSIONS
  Our findings strongly confirm SNCA and MAPT as major PD susceptibility genes for idiopathic PD in the Italian population. Interaction analyses did not evidence either epistatic effects between the two loci or gene-environment interactions.
authors: Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan, Italy.
authors: Luca
authors: L
authors: Trotta
authors: Ilaria
authors: I
authors: Guella
authors: Giulia
authors: G
authors: Soldà
authors: Francesca
authors: F
authors: Sironi
authors: Silvana
authors: S
authors: Tesei
authors: Margherita
authors: M
authors: Canesi
authors: Gianni
authors: G
authors: Pezzoli
authors: Stefano
authors: S
authors: Goldwurm
authors: Stefano
authors: S
authors: Duga
authors: Rosanna
authors: R
authors: Asselta
mesh_terms: D000368:Aged; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins