CYBB and rheumatoid arthritis: Importantly, polymorphism of the Ncf1 gene, either through a single nucleotide polymorphism or by a copy number variation, has been shown to be a major genetic cause of autoimmune diseases such as systemic lupus erythematosus and RA [20] and similar to mutations in mice and rats, the mutation in the human Ncf1 gene leads to NOX2 dysfunction.