TAS2R38 genotype and CRS severity in children with cystic fibrosis.

Abstract

Background: Cystic fibrosis is a heterogeneous disease whose severity and symptoms largely depend on the functional impact of mutations in the cystic fibrosis transmembrane conductance regulator gene. Other genes may also modulate the clinical manifestations and complications associated with cystic fibrosis. Genetic variants of the bitter taste receptor TAS2R38 have been shown to contribute to the susceptibility and severity of chronic rhinosinusitis. This study aims to elucidate the role of TAS2R38 as a novel modifier gene influencing sinonasal disease severity and pulmonary Pseudomonas Aeruginosa colonization in children with cystic fibrosis.

Methods: This retrospective observational case-control study evaluated sinus clinical features, quality of life, and the occurrence of Pseudomonas Aeruginosa pulmonary colonization in 69 children with cystic fibrosis. Propylthiouracil testing and TAS2R38 genotyping were performed to characterize patients based on receptor functionality.

Results: The non-taster genetic variant of bitter taste receptor TAS2R38 was associated with greater severity of chronic rhinosinusitis, as measured by endoscopic and radiological scores, compared to the taster variant (p = 0.031 and p = 0.03, respectively). Furthermore, an inverse correlation was observed between the age at first Pseudomonas Aeruginosa infection and chronic rhinosinusitis severity assessed by endoscopic score (r = -0.3388, p = 0.0302).

Conclusions: The findings highlight the role of TAS2R38 as a potential genetic modifier influencing the severity of chronic rhinosinusitis in children with cystic fibrosis. The clinical implications include the potential development of T2R38-targeted topical therapies and the use of taste testing or genotyping to predict susceptibility to infection. In addition, these results may pave the way for novel, tailored therapeutic approaches in the era of precision medicine.