Anatomical sampling site is not associated with TAS2R38 gene expression in chronic rhinosinusitis: A cross-sectional RT-qPCR study.

BACKGROUND

Chronic rhinosinusitis (CRS) is a complex inflammatory condition affecting the sinonasal mucosa. The bitter taste receptor T2R38 (encoded by TAS2R38) is expressed on ciliated respiratory epithelial cells, detecting bacterial quorum-sensing acyl-homoserine lactones to stimulate nitric oxide production and accelerate mucociliary clearance. However, whether mucosal TAS2R38 transcript levels vary across distinct sinonasal anatomical niches remains unverified, raising concerns regarding potential sampling bias in translational airway research.

OBJECTIVE

To determine whether sinonasal mucosal TAS2R38 gene expression differs across anatomical sub-sites in patients with CRS undergoing functional endoscopic sinus surgery (ESS) and evaluate variance contributions between individual host biology and biopsy sites.

METHODS

In this prospective cross-sectional study, 337 mucosal specimens were harvested from up to six anatomical sites (inferior turbinate, maxillary, ethmoid, frontal, and sphenoid sinuses, and nasal polyps) in 67 surgical CRS patients (EPOS 2020 criteria), alongside 29 non-inflammatory septal control specimens. Relative TAS2R38 mRNA expression was quantified by MIQE-compliant RT-qPCR normalized to GAPDH. Clustered paired [Formula: see text]data were evaluated using linear mixed-effects modeling with patient-specific random intercepts as the principal analytical framework, alongside sensitivity analyses and fold-difference calculations ([Formula: see text]).

RESULTS

Following quality control (excluding 84 specimens due to strict cycle thresholds and minute fibrous tissue yield), 253 valid specimens across 55 patients were analyzed (inferior turbinate: n = 52; maxillary: n = 50; ethmoid: n = 49; polyps: n = 44; frontal: n = 43; sphenoid: n = 15). Mean [Formula: see text]values were comparable across subsites (range: 2.06 to 2.81; exploratory ANOVA F = 0.42, P = 0.834). In the principal linear mixed-effects model, anatomical sampling site was not associated with TAS2R38 expression ([Formula: see text]). Inter-individual biological variance ([Formula: see text]; ICC = 0.333) substantially exceeded intra-individual spatial variation. Robustness was verified across six sensitivity scenarios, including the exclusion of sphenoid tissues and multivariable adjustments for age and sex (P = 0.617). Diseased mucosa demonstrated an exploratory 2.48-fold upregulation relative to non-site-matched septal controls.

CONCLUSION

Mucosal TAS2R38 mRNA expression shows no statistically significant association with anatomical sampling site in surgical CRS, with transcript variability driven predominantly by between-patient biological differences. These findings provide translational evidence supporting the potential utility of inferior turbinate biopsy as a pragmatic, accessible surrogate for investigating sinonasal chemosensory innate defense.