Parkinson’s disease (PD) is the most common neurodegenerative disorder affecting movement, with oxidative stress recognised as one of the key factors contributing to PD development. The functionality of antioxidant enzymes such as the superoxide dismutases (SODs) are known to be modified by genetic polymorphism, impacting organisms’ capacity to respond to oxidative stress and properly remove free radicals. The association between SOD gene variability and increased risk for development of PD is not clear. In humans, there are over 3,400 SOD1 gene variants with varying sequence similarity. This study aims to identify and characterise specific SOD1 gene variants predicted to have a deleterious impact on enzyme function with the potential association to PD development and progression.
Using in silico methods, publicly available databases (NCBI and UniProt) over 30,000 SOD1 variants were detected and genetic polymorphism variability included: missense, synonymous, and frameshift variants. Thirteen out of eighty variants were predicted to have the greatest adverse impact on enzyme function based on NCBI records of clinical significance and SnpEff variant impact predictions. These variants were selected for the evaluation of their predicted impact on SOD1 protein structure and function using InterProScan and Swiss-Model. The most harmful mutation types were found to be frameshift and missense variants, causing loss of important domains or major changes in the domains of the resulting predicted SOD1 proteins.
Our findings reveal new knowledge about genetic SOD polymorphism, and provide an overview of existing genetic variations and the in silico implication on functional domains, which may impact diseases linked to oxidative stress such as PD. In silico analyses revealed a small list of likely-harmful SOD variants. Follow-up case-control studies are needed to assess the presence of the identified SOD1 variants in the PD population and determine whether those specific variants increase oxidative stress and the risk of PD.