Polymorphisms In Tlr9 Gene Influence Response To Corticosteroids In Severe Chronic Rhinosinusitis

Decreased levels of TLR9 on the epithelium of the sinus mucosa are noted in a subpopulation of patients with chronic rhinosinusitis (CRS) unresponsive to endoscopic sinus surgery (ESS) and pre-operative oral corticosteroid therapy. We wished to determine whether polymorphisms in TLR9 influencing response to corticosteroids might explain this phenomenon. A population of 206 patients with refractory CRS (defined as a poor response to one ESS or more than one ESS regardless of outcome) and 196 postal-code matched controls were recruited and blood drawn for DNA. A maximally informative set of single nucleotide polymorphisms (SNPs) for the TLR 9 gene were selected from the HapMap dataset and genotyped. Patients were stratified according to medication required for disease control using a standardized treatment algorithm of progressively increasing strength corticosteroid therapy administered by a single physician: intranasal corticosteroids only (MILD), corticosteroid irrigations (MODERATE) or other agents (oral prednisone, intermittent or continuous antibiotics or uncontrolled disease) (SEVERE). Logistic regression analysis was used to determine association between genotype and phenotype. No difference in genotype frequencies was observed between patients and controls. However, 3 SNPs were identified as potentially associated with response to medication (rs352162: CT allele: Odds ratio (OR) 1.44, CC: OR 1.76, p = 0.0005, rs352140: TC: OR 1.12, TT: OR 1.67, p = 0.001, rs352143; GA: OR 1.37, GG: OR 1.86, p = 0.002). These results suggest that polymorphisms in TLR9 influence response to corticosteroids in refractory CRS. A second cohort is currently under study to confirm these results.