A Replication Study Validates The Association Of 14 Snps In 11 Genes With Chronic Rhinosinusitis With Nasal Polyposis

RATIONALE: We have previously identified several single nucleotide polymorphisms (SNPs) associated with chronic rhinosinusitis (CRS). However, to date, only one genetic association has been replicated in the literature (rs17561, IL1A gene). The goal of this study is to replicate our previous findings in a second population of CRS with nasal polyps (CRSwNP). METHODS: 409 Caucasian patients with CRSwNP and 190 postal-code matched controls were prospectively recruited from an academic sinus practice. DNA was extracted from blood and used to perform a pooling-based genome-wide association study (pGWAS) with the Illumina Human 1M array in 4 replicates. From these pooled results and from our previously reported SNPs associated with CRS, 78 high priority SNPs were selected for individual genotyping using the Sequenom platform. Association tests were performed using the PLINK software. RESULTS: 72 out of 78 SNPs were genotyped successfully. In this second population, a total of 14 SNPs in 11 genes were identified. By allelic association, 10 SNPs in 8 genes were associated with CRS (0.002 < p-value< 0.05; OR <0.70 and OR >1.58). When assessed for genotype specific effects, 14 SNPs in 11 genes were associated (HMZ: 11 SNPs, 9 genes; p= 0.0065 - 0.043, OR <0.42 and OR >2.28) (HTZ: 4 SNPs, 4 genes; p= 0.042 - 0.041, OR <0.54 and OR >1.78). CONCLUSIONS: We validate several new polymorphisms in a second population. Further functional studies are required to better understand the mechanisms by which these genes are implicated in the pathophysiology of CRSwNP.