A pooling-based genome-wide association study implicates the p73 gene in chronic rhinosinusitis

Abstract

Background: p73 is a gene that may confer a genetic susceptibility to the development of chronic rhinosinusitis. Objective: To verify an association between p73 and chronic rhinosinusitis, identified in a pooling-based genome-wide association study in a human population. Methods: Prospective recruitment of 206 patients and 196 postal code-matched controls. DNA extraction, followed by pooling, high-density single nucleotide polymorphism (SNP) genotyping, and individual genotyping, was carried out. Gene sequencing was carried out in 10 patients and 1 control. Results: Statistical analysis of SNP rs3765731 revealed a significant difference in minor allele frequency between the case and control groups.Minor allele A wasmore frequent in the healthy group, with an odds ratio of 0.6533, whereas G had a higher association with the disease state. Subgroup analysis of allele frequencies showed A to be associated with a lesser likelihood of developing chronic rhinosinusitis. Homozygous AA patients with severe disease had a sevenfold lesser risk of chronic rhinosinusitis compared with GG homozygotes (odds ratio 0.14). Sequencing did not reveal any amino acid changes conferring a change of function in secreted proteins. Conclusion: We have demonstrated an association between rs3765731 and chronic rhinosinusitis. Minor allele A has a protective effect compared with major allele G. Interaction with other signaling proteins and induction of other genes will better explain this mechanism. © 2010 The Canadian Society of Otolaryngology-Head & Neck Surgery.