A Pooling-Based Genome-Wide Association Study Implicates the p73 Gene in Chronic Rhinosinusitis

作者：Tournas Athanasios^*; Mfuna Leandra; Bosse Yohan; Filali Mouhim Abdelali; Grenier Jean Paul; Desrosiers Martin

来源：Journal of Otolaryngology-Head & Neck Surgery, 2010, 39(2): 188-195.

DOI：10.2310/7070.2009.090080

• chronic rhinosinusitis
• genome-wide association study
• p73
• single nucleotide polymorphism
• TP73

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 was more 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.

• 出版日期2010-4