Direct Maxillary Sinus Tissue Analysis for T2R38 Polymorphisms: Establishing a Translational Framework in Odontogenic Rhinosinusitis

Bitter taste receptors (T2Rs), specifically T2R38, are present in the respiratory epithelium and react with bacterial quorum-sensing molecules to induce an innate immunity response. Although T2R38 polymorphisms have been correlated with susceptibility to chronic rhinosinusitis (CRS), they have not yet been explored in odontogenic rhinosinusitis (ORS), a distinct form of CRS with particular microbial and inflammatory features. Objectives: We aim to establish a proof-of-concept methodology for investigating T2R38 genetic variants in ORS using direct maxillary sinus tissue analysis and demonstrate the feasibility of this translational approach. Methods: We conducted a prospective case-control study of 36 ORS patients and 37 controls undergoing septoplasty without sinonasal disease. Maxillary sinus mucosal biopsies were obtained intraoperatively with informed consent. Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit and quantified via NanoDrop spectrophotometry. T2R38 haplotypes were determined and classified as taster (PAV/PAV), non-taster (AVI/AVI), or intermediate (PAV/AVI) phenotype. Results: T2R38 phenotype distributions between ORS patients and controls were: tasters 11.1% vs 18.9%, non-tasters 27.8% vs 18.9%, and intermediate phenotypes 50.0% vs 37.8%, respectively. Statistical analysis revealed no significant association between T2R38 phenotypes and ORS susceptibility (Pearson χ² = 0.372, df = 1, p = 0.542; Fisher's exact test p = 0.595). The effect size was minimal (φ = 0.07). Non-taster phenotype showed a non-significant trend toward higher prevalence in ORS patients (OR = 1.4, 95% CI: 0.5–3.9, p > 0.5), though this finding lacks statistical power given the sample size. Conclusion: This proof-of-concept study successfully demonstrates the feasibility of T2R38 genotyping from maxillary sinus mucosa in ORS patients, establishing a novel methodological framework for investigating genetic factors in odontogenic sinonasal disease. While preliminary findings suggest potential phenotype differences (non-taster prevalence: 27.8% vs 18.9%), the study's primary value lies in validating the translational approach and informing power calculations for definitive multicenter investigations. This methodology provides the foundation for future studies to elucidate the role of taste receptor genetics in ORS pathogenesis and potentially guide personalized therapeutic strategies.