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


CONCLUSIONS
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.
Tournas
Athanasios
A
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Québec. athanasios.tournas@mail.mcgill.ca
Mfuna
Leandra
L
Bossé
Yohan
Y
Filali-Mouhim
Abdelali
A
Grenier
Jean-Paul
JP
Desrosiers
Martin
M
D000483:Alleles; D016022:Case-Control Studies; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012220:Rhinitis / Q000235:genetics*; D012852:Sinusitis / Q000235:genetics*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins