Abstract
Objective
Recently, a pooling-based genome wide association (pGWAS) scan idenfied the interleukin-22 receptor alpha 1 (IL22RA1) gene as a promising candidate for chronic rhinosinusitis (CRS). The relevance of this gene in CRS is also substantiated by previous biological studies 1) that stimulation of the gene product increases the innate immune responses in some inflammatory diseases, and 2) a reduced level of the gene transcript in patients with recalcitrant CRS with nasal polyposis. We explore whether single nucleotide polymorphisms (SNPs) in the IL22RA1 gene are associated with CRS.
Methods
DNA extracted from a population of 206 patients with severe CRS and 196 postal-code matched controls was used. The 23 tagging SNPs in the IL22RA1 gene were selected from positive results in the pGWAS and completed with tagging SNPs from the CEU HapMap dataset and genotyped in our population. The haploview software was used to determine association.
Results
22 SNPs were genotyped successfully with a genotype distribution in agreement with the Hardy-Weinberg equilibrium. Seven (rs10751768, rs10794665, rs16829225, rs3936073, rs4292900, rs4648936, rs7418238) out of 22 genotyped-SNPs were significantly associated with CRS (p-value: 0.0009 to 0.0337; OR: 1.44 to 1.76).
Conclusions
Polymorphisms in the IL22RA1 gene are associated with severe CRS. This may help better understand the pathophysiology of CRS and identify new targets for therapy. Replication in a second population with CRS is in progress to validate these findings.
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