Effect of A - G transition at position –21 of intron 10 of NCF-2 gen on p67-phox expression

Abstract

Phagocytic cells (neutrophils, eosinophils, monocytes and macrophages) produce reactive oxygen species (ROS) which have important microbicidal activity. The generation of these molecules occurs during the respiratory burst phenomenon,which depends upon the activation of an enzymatic system known as NADPH oxidase. The importance of this system has been shown through the study of chronic granulomatous disease, because with this disease the enzymatic complex is disrupted, which alters microbicidal mechanisms and leads to recurrent infections. This disorder is caused by mutations in any of the genes encoding the components of the NADPH oxidase complex. In addition to these mutations, several polymorphisms have been described for these genes. However, these nucleotide changes have not been associated with greater susceptibility to infections. Recently, we described the A→G substitution at position –21 in the extreme 3’ end of intron 10 of the NCF-2 gene as a possible polymorphism. Because this sequence belongs to the branch point sequence necessary for pre-mRNA splicing and a previous study showed skipping of exon 11 of the p67-phox mRNA, we analyzed the protein p67-phox expression in subjects carrying the different genotypes (A/A, A/G and G/G) in the position –21 of the 3 ́ end of intron 10.