Evidence of Association of Interleukin-1 Receptor-Like 1 Gene Polymorphisms with Chronic Rhinosinusitis

Abstract

Background Chronic rhinosinusitis (CRS) is a common complex respiratory disease, with a potential genetic component to its development. The protein encoded by the Interleukin-1 receptor-like 1 (IL1RL1) gene is an important effector molecule of T-helper type 2 responses and may potentially be involved in the persistent inflammatory process observed in CRS. We investigated whether certain polymorphisms in the IL1RL1 gene are differentially present in patients with surgery-unresponsive CRS and in control subjects. Methods DNA extracted from an existing population of 206 adult patients with surgery-unresponsive CRS and 196 postal-code-matched controls was used. A set of 15 tagging single nucleotide polymorphisms (SNPs) was selected from the HapMap data set and genotyped. DNA sequencing was performed in a subgroup of 15 CRS patients. Results Statistically significant allelic associations with CRS were noted for 5 SNPs (rs10204137, p = 0.04; rs10208293, p = 0.03; rs13431828, p = 0.008; rs2160203, p = 0.03, and rs4988957, p = 0.03). The analysis showed a consistent significant protective effect against CRS for all the SNPs, yielding an odds ratio (OR) ranging from 0.56 to 0.72. The loci rs13431828 showed the highest association with CRS (p = 0.008; OR = 0.56; 95% CI, 0.36–0.86). A subanalysis revealed that the observed associations were stronger among patients with more severe disease. Sequencing identified five additional known nonsynonymous coding SNPs in linkage disequilibrium with genotyped SNPs. Conclusion Pending replication of these results, this study suggests that polymorphisms within the IL1RL1 gene may be associated with CRS, conferring a protective effect, particularly among those with severe disease.