Analysis of TAS2R bitter taste receptors expression in the nasal epithelium of asthma patients by nextgeneration sequencing

Introduction. Bitter taste receptors (TAS2R) are a family of receptors consisting of 25 members expressed in various organs and tissues of the body. Despite the high potential of TAS2R agonists as therapeutic agents for the treatment of asthma, there are only a few studies describing the expression of these receptors in asthma.

Aim. To conduct a comparative analysis of the full spectrum of TAS2R genes expressed in the nasal epithelium of healthy individuals and patients with asthma, as well as to identify TAS2R associated with the disease characteristics.

Materials and methods. The study included 23 patients with asthma (mean age 41.4 ± 3.15 years), predominantly of moderate severity, and 8 healthy volunteers (mean age 38.4 ± 1.67 years). Cells for analysis were obtained via brush biopsy from the inferior nasal turbinate. mRNA expression was analyzed using next-generation sequencing (NGS) on MGISEQ-200 sequencer. Pulmonary function was assessed using spirometry. Asthma control was evaluated using the Asthma Control Test (ACT) questionnaire.

Results. Among the patients with asthma, expression of TAS2R4, TAS2R5 and TAS2R20 was detected in 100% of the samples; other highly expressed genes included TAS2R38, TAS2R14, TAS2R19 and TAS2R31. In the control group, only TAS2R20 was consistently detected, while TAS2R4, TAS2R5, TAS2R14, TAS2R10 and TAS2R38 were expressed less frequently but at least in half of the samples. Expression of TAS2R9, TAS2R16 and TAS2R43 was completely absent both in asthma and control samples. TAS2R20 was expressed 1.6-fold higher in patients with asthma compared to the control group (FDR p=0.07), and inversely correlated with disease control (ρ = -0.74, FDR p = 0.001). Expression of TAS2R4 and TAS2R5 was inversely correlated with airway patency, particularly with FEF₅₀ (FDR p = 0.04) and MEF_25-75 (FDR p = 0.01).

Conclusion. TAS2R4, TAS2R5, and TAS2R20 receptors, which show the most stable and high mRNA expression in the nasal epithelium of patients with asthma, are of the greatest interest for further study. Expression of TAS2R20 is associated with asthma and increases as the disease control decreases, while TAS2R4 and TAS2R5 undergo upregulation in individuals with more pronounced bronchial obstruction. 

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