There is evidence that genetic polymorphism in SPRR genes may predict the development of asthma in children with atopy and, correlatively, that expression of SPRRs increased under allergic conditions, which leads to epithelial barrier dysfunction in atopic disease.

RNAs from uncinate tissue specimens from patients with CRS and control subjects were compared by RNA sequencing using Ingenuity Pathway Analysis and quantitative PCR. Researchers examined a separate cohort of archived sinus tissue by immunohistochemistry.

A statistically significant increase of SPRR expression in CRS sinus tissue was identified as not a result of atopic presence. SPRR1 and SPRR2A expressions were markedly increased in patients with CRS on RNA sequencing, with confirmation using real-time PCR. Immunohistochemistry of archived surgical samples demonstrated staining of SPRR proteins within the squamous epithelium of both groups. Pathway analysis indicated TNF alpha as a master regulator of the SPRR gene products.

The study concluded that expression of SPRR1 and SPRR2A are increased in mucosal samples from patients with CRS and appeared as a downstream result of TNF alpha modulation, which possibly resulted in epithelial barrier dysfunction.