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Anatomical Sampling Site Is Not Associated with TAS2R38 Gene Expression in Chronic Rhinosinusitis: A Cross-Sectional RT-qPCR Study

This cross-sectional RT-qPCR study demonstrates that TAS2R38 gene expression is uniform across various sinonasal anatomical sites in chronic rhinosinusitis patients, indicating that easily accessible tissues like the inferior turbinate are representative for molecular sampling without the need for site-specific biopsies.

Original authors: Xuan Nam Nguyen, Anh Luong Thi Lan, Minh Thanh Cao

Published 2026-09-15

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CC BY 4.0

Original authors: Xuan Nam Nguyen, Anh Luong Thi Lan, Minh Thanh Cao

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

Inside the human nose, the lining of the airways does more than just filter dust and warm the air we breathe; it acts as a vigilant sentry, constantly scanning for invisible invaders. This frontline defense relies on a specific family of proteins known as bitter taste receptors. While these receptors are famous for helping the tongue detect bitter flavors in food, a different version of them, called T2R38, lives on the tiny, hair-like structures that line the sinuses. These receptors function as biological sensors for a specific type of bacteria. When they detect chemical signals released by these germs, they trigger a rapid response: the cells produce nitric oxide, a gas that speeds up the beating of the tiny hairs to flush out mucus and directly attacks the bacterial invaders. This system is a crucial part of the body's innate immunity, the first line of defense that works without needing to learn from past infections.

Chronic rhinosinusitis is a common and frustrating condition where this delicate system fails, leading to long-term inflammation, blockage, and pain. Scientists have long known that variations in the gene responsible for the T2R38 receptor can make some people more susceptible to these infections than others. However, a practical question has lingered in the minds of researchers and surgeons: to understand this defense system in a patient, where exactly should they take a tissue sample? The nose is a complex landscape of different chambers and structures, from the lower turbinates to the deep frontal and sphenoid sinuses. It was unclear whether the level of these protective receptors changed depending on which specific spot was sampled, or if the body maintained a uniform defense strategy across the entire nasal cavity.

To answer this, a team of researchers at Hanoi Medical University conducted a detailed study involving patients undergoing surgery for chronic sinusitis. They collected tissue samples from up to six different locations within the same patient's nose, including the lower turbinate, the maxillary sinus, the ethmoid sinus, the frontal sinus, the sphenoid sinus, and any nasal polyps present. In total, they gathered hundreds of specimens from dozens of patients, carefully measuring the amount of genetic instructions, or mRNA, for the T2R38 receptor in each sample. They compared these findings against tissue from healthy individuals who did not have sinus disease.

The results were remarkably consistent. The researchers found that the levels of the T2R38 receptor were essentially the same regardless of where the sample was taken within the sinuses. Whether the tissue came from the easily accessible lower turbinate or the deep, hard-to-reach sphenoid sinus, the amount of genetic material for this receptor did not vary significantly. The study showed that the differences in receptor levels between different patients were far greater than any differences found between the various spots within a single person's nose. In fact, the disease state itself appeared to drive the levels; the inflamed tissue from patients with chronic sinusitis contained roughly two and a half times more of the receptor's genetic instructions than the healthy tissue from the control group.

This uniformity across the nasal landscape offers a clear path forward for medical research and practice. Because the receptor levels are stable throughout the sinonasal area, scientists and doctors do not need to perform invasive biopsies in deep or delicate sinus cavities to get an accurate picture of a patient's immune defense. A simple sample from the lower turbinate, which is easy to reach and less risky, provides a reliable representation of the entire system. The study confirms that the body's chemical sensing mechanism is a widespread, coordinated effort rather than a patchwork of localized defenses, and that the individual's unique biology plays a much larger role in how this system functions than the specific location of the tissue sample.

Technical Summary: Anatomical Sampling Site Is Not Associated with TAS2R38 Gene Expression in Chronic Rhinosinusitis

Problem Statement
Chronic rhinosinusitis (CRS) is a complex inflammatory condition where the sinonasal epithelium functions as a sentinel organ for innate immunity. A critical component of this defense is the bitter taste receptor T2R38, encoded by the TAS2R38 gene, which detects bacterial quorum-sensing molecules (acyl-homoserine lactones) and triggers nitric oxide (NO) production to enhance mucociliary clearance. While the clinical relevance of TAS2R38 expression levels and genetic variations is established, a significant methodological gap exists: it remains unclear whether TAS2R38 transcript levels vary across different anatomical locations within the sinonasal cavity (e.g., turbinates, various sinuses, and polyps). This uncertainty complicates the standardization of biopsy protocols for molecular airway research, as regional differences in airflow, pathogen load, or tissue structure could theoretically introduce sampling bias.

Methodology
This prospective cross-sectional study was conducted at Hanoi Medical University Hospital between April 2025 and June 2026. The cohort included 67 adult patients diagnosed with CRS according to EPOS 2020 criteria, scheduled for functional endoscopic sinus surgery (ESS), and 29 non-inflammatory control subjects.

Sampling: Up to six anatomical sites were sampled per CRS patient: inferior turbinate, maxillary sinus, ethmoid sinus, frontal sinus, sphenoid sinus, and nasal polyps (if present). A total of 337 specimens were initially collected.
Molecular Analysis: Total RNA was extracted, and cDNA synthesized. TAS2R38 transcript levels were quantified using RT-qPCR with GAPDH as the internal reference. Expression was calculated as $\Delta Cq = Cq(TAS2R38) - Cq(GAPDH)$ .
Statistical Modeling: After strict quality control (excluding samples with $Cq > 35$ or no amplification), 253 valid specimens from 55 CRS patients were analyzed. The primary analysis utilized a linear mixed-effects model with patient-specific random intercepts to account for intra-subject clustering. The model tested the association between anatomical site and $\Delta Cq$ , while calculating the intraclass correlation coefficient (ICC) to decompose variance between individuals versus within individuals across sites. Sensitivity analyses and adjustments for age and sex were also performed.

Key Results

Uniform Expression: The mean $\Delta Cq$ values across all six anatomical sites ranged narrowly from 2.06 (maxillary sinus) to 2.81 (sphenoid sinus). One-way ANOVA revealed no statistically significant differences among sites ( $F = 0.42, P = 0.834$ ).
Mixed-Effects Modeling: The linear mixed-effects model confirmed that the anatomical sampling site was not a significant predictor of TAS2R38 expression ( $\chi^2(5) = 3.58, P = 0.611$ ). Pairwise comparisons against the inferior turbinate reference site showed no significant differences for any other sinus or polyp tissue.
Variance Decomposition: The analysis indicated that inter-individual biological differences were the primary driver of expression variability. The estimated between-patient variance ( $\sigma_u^2 = 1.64$ ) was substantial, yielding an ICC of 0.333. This suggests that approximately one-third of the total transcript variability is attributable to patient-specific factors, while variation within a single patient across different anatomical regions is minimal.
Disease vs. Control: Relative expression analysis showed that TAS2R38 mRNA levels in diseased CRS mucosa were 2.48 times higher than in non-inflammatory control tissues.
Robustness: These findings remained consistent across six sensitivity analyses, including scenarios excluding polyps, sphenoid specimens, or extreme residuals, and after adjusting for age and sex.

Significance and Claims
The study concludes that TAS2R38 mRNA is expressed uniformly and widely throughout the major sinonasal areas and nasal polyps in CRS patients. The authors assert that the anatomical sampling site does not act as a confounding factor when quantifying mucosal TAS2R38 genes.

Consequently, the paper claims that researchers and clinicians can reliably use more accessible tissues, such as the inferior turbinate, as a representative surrogate for the entire paranasal sinus system in molecular studies. This finding supports the simplification of biopsy protocols, allowing for the avoidance of more invasive sampling in delicate sinus regions without compromising the validity of molecular data regarding sinonasal chemosensory innate defense. The study emphasizes that future research should focus on patient-specific biological drivers (such as genotype and endotype) rather than anatomical location when investigating TAS2R38 expression.

Technical Summary: Anatomical Sampling Site Is Not Associated with TAS2R38 Gene Expression in Chronic Rhinosinusitis

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