Mutations of the alpha-synuclein gene have shown to be relevant in some rare 
families with autosomal dominant Parkinson's disease (PD). Furthermore, 
alpha-synuclein protein is a major component of the Lewy bodies also in sporadic 
PD patients. Increased levels of wildtype alpha-synuclein in the cell leads to 
increased intracellular hydrogen peroxide levels and causes death of 
dopaminergic neurons in rat primary culture. Subsequently, oxidative stress has 
been directly linked with alpha-synuclein aggregation in vitro. This raises the 
question whether increased alpha-synuclein expression might be linked to higher 
susceptibility to PD and whether alpha-synuclein promoter polymorphisms are 
associated with PD. Here, two polymorphisms (-116C>G and -668T>C) of the 
alpha-synuclein promoter defining four haplotypes have been characterized in 315 
German PD patients. The influence of the four haplotypes on gene expression was 
studied by CAT reporter gene assays in neuronal SK-N-AS cells. The -668C/-116G 
haplotype revealed significant higher CAT expression than the -668T/-116G or the 
-668T/-116C haplotype, respectively. Although the -668C/-116G haplotype was more 
common in PD patients, this difference was not significant.