DNA Methylation Association in Chronic Rhinosinusitis with Nasal Polyps - Epigenetic Study

• Grant number: 24/03356-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Wilma Terezinha Anselmo Lima
• Grantee: Wilma Terezinha Anselmo Lima
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Edwin Tamashiro ; Fabiana Cardoso Pereira Valera ; Leandro Machado Colli ; Tathiane Maistro Malta Pereira

Abstract

Introduction: Despite the possibility of phenotypic distinction in chronic rhinosinusitis (CRS) with or without nasal polyps (NP), patients respond differently to available treatments, whether clinical and/or surgical, denoting a distinct range of endophenotypes. It is essential to identify biomarkers that, in addition to helping in the selection of patients who will benefit from new therapeutic weapons, as in the case of biologicals, also help predict the response. There is strong evidence that exhaled nitric oxide (FENO) values are related to nasal diseases, especially in cases of nasal polyposis. Epigenetics can produce heritable phenotypic changes, without altering the DNA sequence, induced by environmental impact, diet and lifestyle. Studies have demonstrated that changes in DNA methylation can contribute to the pathophysiology of CRS, such as regulating the transcription of some TH genes and the production of cytokines. Thus, the premise that chronic rhinosinusitis can be the result of interactions between a genetically susceptible individual and the environment makes epigenetics a promising field of study in understanding the pathophysiology of this disease, to prevent, diagnose and identify possible therapeutic targets. Objectives: To identify genome-wide differences in DNA methylation in patients with CRSwNP and compare with the control group. Correlate possible environmental factors of home and occupational exposure or habits of patients with CRSwNP, compared to controls. Correlate the FeNO values found with the severity of the disease, predicting it as a valuable biomarker. Methods: After approval by the research ethics committees, 50 patients with CRSwNP and 50 controls with an indication for rhinoseptoplasty will be selected at the outpatient clinic of the Specialized Center for Otorhinolaryngology and Speech Therapy (CEOF) at HCFMRP-USP, aged between 18 and 70 years. Both will answer a questionnaire to outline the age, socioeconomic, environmental, and occupational exposure profile of the participants. In the first group, nasal polyps will be collected during routine nasofibroscopy, and in the second, middle turbinate mucosa will be collected during surgery. The samples will be sent to the biorepository at the Blood Center (HCFMRP-USP), where DNA will later be extracted and analysis for the presence of methylation will be carried out, correlating the possible findings with the severity of CRS and with the data extracted from the questionnaire. The FENO test will be carried out on an outpatient basis, and the indices found will be correlated with the degree of severity of the disease under study. Rationale: The identification of possible genetic and environmental mechanisms that may influence the manifestation and severity of CRS can assist in prevention, diagnosis, and treatment, since epigenetic changes can be therapeutically reversed. Nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FENO) measurements are an objective measurement of type 2 airway inflammation. This makes FeNO an important biomarker, which can indicate disease severity and predict response to treatment. Its importance in asthma is already well established, with studies still lacking for chronic rhinosinusitis with nasal polyps.Key wordsChronic rhinosinusitis, nasal polyps and methylation, exhaled nitric oxide (AU)