Overexpression of leukotriene C4 synthase (LTC4S) and plasminogen activator inhibitor 1 (PAI-1) gene promoter polymorphisms in sinusitis

Abstract

Rationale We have investigated the genetic predisposition of two forms of sinusitis: chronic hyperplastic eosinophilic sinusitis (CHES) and chronic inflammatory sinusitis (CIS). Studies have described polymorphisms in genes involved with both leukotriene synthesis and remodeling. A polymorphism in the promoter of the LTC4S gene has been identified that is a C-to-A base exchange that influences gene expression. The PAI-1 gene has been associated with tissue fibrosis and could be involved in polyp formation. This gene has a polymorphism consisting of either 4G or 5G residues in the promoter which alters transcription of the PAI-1 gene. We have investigated the role of these polymorphisms in CHES and CIS. Methods DNA was obtained from patients undergoing nasal polyp surgery or from control donors with no history of sinus disease. Polyp tissue underwent blinded pathological examination and scored for the presence of eosinophils. Polyps were classified into two groups based on the presence (CHES) or the absence of eosinophils (CIS). DNA was analyzed for the LTC4S or PAI-1 promoter polymorphisms. Results Our studies demonstrated that the A allele for the LTC4S gene was found at a higher frequency in patients with both CHES and CIS (q=0.28) when compared to a control group without disease (q=0.19) consistent with the described expression of leukotrienes. The 4G allele of the PAI-1 gene promoter was found at a higher frequency in patients with CIS (q=0.56) when compared to controls (q=0.38) or CHES (q=0.43). Conclusions There appears to be a genetic component that contributes to nasal polyp formation in sinusitis.