Scientific Oral Presentations: Pathophysiology and Mechanisms
ARS054 - Denatonium-responsive bitter receptors and AERD
Friday, April 29, 2022
11:27 AM – 11:33 AM CT
Location: Landmark C
Corrine Mansfield; Katherine Bell; Michael Kohanski, MD; John Bosso, MD; Nithin Adappa, MD, FARS; James N. Palmer, MD, FARS; Noam Cohen, MD, FARS; Ralph Butler, Professor; Danielle Reed, Associate Director
Background: Aspirin-exacerbated respiratory disease (AERD) consists of a unique endotype of chronic rhinosinusitis with nasal polyposis, and asthma, with accompanying aspirin/NSAID sensitivity. Genetic variation in bitter receptors (T2Rs) on ciliated cells (e.g., T2R38) influences susceptibility to CRS without nasal polyposis (CRSsNP). The solitary chemosensory cell (SCC) also expresses T2Rs and participates in the Th2 inflammatory response typical of AERD. AERD patients show enhanced bitterness sensitivity to denatonium benzoate (DB), and nasal polyps appear enriched in SCCs. Here we investigate whether AERD patients exhibit genetic variation in DB-sensitive T2Rs.
Methods: Subjects with AERD and CRSsNP were enrolled at a quaternary academic rhinology practice. Demographic and clinical information was collected. All were genotyped using an OpenArray gene chip containing SNPs within the DB-responsive T2Rs genes.
Results: 35 patients with AERD and 24 patients with CRSsNP were identified (54% female, mean age of 51 years). One SNP within TAS2R46 (rs2708381) showed a significant between-group difference with AERD subjects having greater T nucleotide frequency compared with CRSsNP (23.1% vs 20.5%; p=0.013). The remaining DB-responsive T2Rs showed no significant differences (TAS2R4; TAS2R8; TAS2R10, TAS2R13).
Conclusion: Exploratory data shows the gene encoding T2R46 in AERD has greater T nucleotide frequency than CRSsNP; the remaining DB-responsive T2Rs showed no significant differences. This result may be due to limited statistical power. Additional studies are necessary to better characterize the role of SCCs on the pathophysiology of AERD.