Association of IL1A, IL1B, and TNF Gene Polymorphisms With Chronic Rhinosinusitis With and Without Nasal Polyposis

<h3>Objective</h3> To replicate and extend recent findings in a Turkish population of associations between chronic rhinosinusitis (CRS) with nasal polyposis and single-nucleotide polymorphisms (SNPs) in the<i>IL1A</i>(rs17561 and Ser114Ala),<i>IL1B</i>(rs16944), and<i>TNF</i>(rs361525 and rs1800629) genes. <h3>Design</h3> In a case-control replication study, DNA samples were obtained from 206 patients with severe CRS (cases) and from 196 postal code–matched controls. For<i>IL1A</i>and<i>TNF</i>, the 3 reported SNPs were complemented with tagging SNPs using an International HapMap genotyping data set to ensure complete genetic coverage. For<i>IL1B</i>, only the single reported SNP was assessed. A total of 24 SNPs (7 in<i>IL1A</i>, 1 in<i>IL1B</i>, and 16 in<i>TNF</i>) were individually genotyped. The PLINK software package was used to perform genetic association tests. <h3>Setting</h3> Academic research. <h3>Patients</h3> Canadian population of individuals with severe CRS. <h3>Main Outcome Measures</h3> Allelic differences between cases and controls. <h3>Results</h3> Significant allelic differences between cases and controls were obtained for<i>IL1A</i>rs17561 (odds ratio [OR], 1.48;<i>P</i> = .02). The following 3 additional SNPs in this gene were associated with CRS: rs2856838 (OR, 0.63;<i>P</i> = .003), rs2048874 (OR, 0.57;<i>P</i> = .01), and rs1800587 (OR, 1.49;<i>P</i> = .02). These 3 SNPs remained significant after correction for multiple testing. No association was found with<i>IL1B</i>or<i>TNF</i>. <h3>Conclusions</h3> We replicated the previously reported association between the<i>IL1A</i>polymorphism and severe CRS and identified 3 potential new associations in the same gene. This further supports the potential contribution of<i>IL1A</i>to the development of CRS. We were unable to replicate previous reports of associations with<i>IL1B</i>or<i>TNF</i>.

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