Genetic Contribution of CFTR Mutations to Chronic Bronchitis in Children: A Case-Control Study

Masharipova M. S. ¹*, Xalimbetov G. S. ¹, Khasanova D. A. ¹, Nurmuxamedova Rohatoy Abdisharipovna ¹

This study determined the CFTR mutations' role in pediatric chronic bronchitis, advancing understanding and paving the way for predictive genetic medicine.

Abstract

Background: Chronic bronchitis and bronchial asthma are significant respiratory conditions with complex etiologies influenced by genetic and environmental factors. Mutations in the CFTR gene have been implicated in severe respiratory diseases, underscoring the need to explore their association with these conditions. Methods: This study included 150 children with chronic bronchitis and bronchial asthma, alongside a control group of 60 healthy children. Clinical and genealogical analyses were conducted to evaluate hereditary predisposition. Molecular genetic studies focused on eight common CFTR mutations (F508del, W1282X, and N1303K) using RT-PCR with real-time detection. Statistical analyses, including Hardy-Weinberg equilibrium testing and odds ratio calculations, assessed genetic associations. Results: A hereditary predisposition was identified in 32.3% of parents of affected children. Among the patients, heterozygous CFTR mutations were detected, with F508del in 6.25%, W1282X in 2.1%, and N1303K in 2.1%. These findings suggest a strong genetic influence in the studied population. Conclusion: This study reinforces the role of CFTR mutations in chronic bronchitis and bronchial asthma, highlighting the genetic basis of these conditions. Future research should explore additional candidate genes and unidentified CFTR variants to enhance predictive medicine and personalized treatment strategies.

Keywords: CFTR mutations, chronic bronchitis, hereditary predisposition, pediatric respiratory diseases, genetic etiology

References

Barben, J., et al. (2021). Updated guidance on the management of children with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID). Journal of Cystic Fibrosis, 20(5), 810–819. https://doi.org/10.1016/j.jcf.2020.11.006

Diab Cáceres, L., & Zamarrón de Lucas, E. (2023). Cystic fibrosis: Epidemiology, clinical manifestations, diagnosis, and treatment. Medicina Clínica, 161(9), 389–396. https://doi.org/10.1016/j.medcli.2023.06.006

Gembitskaya, T., Chermensky, A., Boitsova, E., & B., E. (2012). Cystic fibrosis today: Progress and problems, promises of etiopathogenetic therapy. Vrach, 23(2).

Kesimer, M., Drummond, M. B., & Boucher, R. C. (2021). Mucus hypersecretion, hyperconcentration, and chronic bronchitis. In Encyclopedia of Respiratory Medicine (2nd ed., Vol. 2, pp. 594–610). https://doi.org/10.1016/B978-0-08-102723-3.00039-1

Miravitlles, M., et al. (2024). Potential systemic effects of acquired CFTR dysfunction in COPD. Respiratory Medicine, 221. https://doi.org/10.1016/j.rmed.2023.107499

Raju, S. V., Solomon, G. M., Dransfield, M. T., & Rowe, S. M. (2016). Acquired cystic fibrosis transmembrane conductance regulator dysfunction in chronic bronchitis and other diseases of mucus clearance. Clinics in Chest Medicine, 37(1), 147–158. https://doi.org/10.1016/j.ccm.2015.11.003

Ramananda, Y., Naren, A. P., & Arora, K. (2024). Functional consequences of CFTR interactions in cystic fibrosis. International Journal of Molecular Sciences, 25. https://doi.org/10.3390/ijms25063384

Roesch, E. A., Nichols, D. P., & Chmiel, J. F. (2018). Inflammation in cystic fibrosis: An update. Pediatric Pulmonology, 53(S3), S30–S50. https://doi.org/10.1002/ppul.24129

Solomon, G. M., Raju, S. V., Dransfield, M. T., & Rowe, S. M. (2016). Therapeutic approaches to acquired cystic fibrosis transmembrane conductance regulator dysfunction in chronic bronchitis. Annals of the American Thoracic Society, 13(S3), S169–S176. https://doi.org/10.1513/AnnalsATS.201509-601KV