Linking risk conferring mutations in NCF4 to functional consequences in Crohn's disease: Figure 1

We read with interest the paper from Muise et al in which they describe a rare variant in the NCF2 gene, which demonstrates a diminished RAC2 binding capacity.1 The NCF2 encoded protein p67phox is one of the components of the NADPH oxidase complex which drives the production of reactive oxygen species (ROS) during the bactericidal response of innate immune cells. Output of disturbed granulocytic ROS as a result of impaired functioning of this enzyme complex has been shown in a number of diseases, including myelodysplasia (MDS) and chronic granulomatous disease.2 3 As Muise and colleagues point out, these diseases have been linked to development of a colitis resembling that seen in Crohn's disease (CD), suggesting a potential role for impaired ROS production in CD pathology. Genome-wide association studies (GWAS) are a promising tool to identify genetic variants …