Cantone Elena, Tosco Antonella, Sepe Angela, Raia Valeria, Negri Rossella, Castaldo Alice, Cimbalo Chiara, Pezzella Paolo, Russo Mario Brandon, Grimaldi Giusi, Di Nola Claudio, Greco Luigi
Department of Neuroscience, Reproductive and Dentistry Science, ENT section, "Federico II University of Naples", Naples, Italy.
Paediatric Unit, Department of Maternal and Child Health, Cystic Fibrosis Regional Reference Center, A.O.U. Federico II, Naples, Italy.
Heliyon. 2025 Jan 7;11(1):e41716. doi: 10.1016/j.heliyon.2025.e41716. eCollection 2025 Jan 15.
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 as a novel modifier gene influencing sinonasal disease severity and pulmonary colonization in children with cystic fibrosis.
This retrospective observational case-control study evaluated sinus clinical features, quality of life, and the occurrence of pulmonary colonization in 69 children with cystic fibrosis. Propylthiouracil testing and TAS2R38 genotyping were performed to characterize patients based on receptor functionality.
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 infection and chronic rhinosinusitis severity assessed by endoscopic score (r = -0.3388, p = 0.0302).
The findings highlight the role of 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.
囊性纤维化是一种异质性疾病，其严重程度和症状很大程度上取决于囊性纤维化跨膜传导调节基因中突变的功能影响。其他基因也可能调节与囊性纤维化相关的临床表现和并发症。苦味受体TAS2R38的基因变异已被证明与慢性鼻窦炎的易感性和严重程度有关。本研究旨在阐明作为一种新型修饰基因在影响囊性纤维化儿童鼻窦疾病严重程度和肺部定植方面的作用。
这项回顾性观察性病例对照研究评估了69例囊性纤维化儿童的鼻窦临床特征、生活质量和肺部定植情况。进行丙硫氧嘧啶测试和TAS2R38基因分型以根据受体功能对患者进行特征描述。
与味觉型变体相比，苦味受体TAS2R38的非味觉型基因变体与慢性鼻窦炎的更严重程度相关，通过内镜和放射学评分衡量（分别为p = 0.031和p = 0.03）。此外，首次感染年龄与通过内镜评分评估的慢性鼻窦炎严重程度之间存在负相关（r = -0.3388，p = 0.0302）。
这些发现突出了作为影响囊性纤维化儿童慢性鼻窦炎严重程度的潜在遗传修饰因子的作用。临床意义包括可能开发针对T2R38的局部治疗方法以及使用味觉测试或基因分型来预测感染易感性。此外，这些结果可能为精准医学时代的新型定制治疗方法铺平道路。
