Interleukin-4 (C590T), Interleukin-6 (174G/C), Interleukin-13 (rs20541) and Tumor Necrotic Factor-α (G308A) Gene Polymorphisms and Clinical Markers as Predictors of Asthma Severity: Insights from a Comparative Study

<bold>Objectives:</bold> This study aims to investigate the link between IL-4, IL-6, IL-13, and TNF-α gene variations and the severity of adult asthma. Methods: Using the PCR-RFLP method, our study investigated gene polymorphisms of IL-4, IL-6, IL-13, and TNF-α in 98 patients with mild asthma, 116 with severe asthma, and 121 healthy volunteers. Results: In the IL-4 gene, the CC genotype protected against mild asthma, while the CT genotype increased its likelihood by threefold. The IL-6 gene's GG genotype increased mild asthma risk fourfold, with GC patterns showing protection. The GG TNF-α gene polymorphism doubled the likelihood of mild asthma but increased severe asthma severity sixfold. AA and AG TNF-α patterns were protective against severe asthma. Patients with severe asthma were older, had higher allergic rhinitis and nasal polyp's rates, and elevated markers of type 2 inflammation, including Total IgE, blood eosinophil counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO). In both unadjusted and adjusted logistic regression models IL-4 gene's recessive model decreased severe asthma risk, but the IL-6 (CC+CG) model predicted severe asthma. TNF-α GG patterns were also a significant predictor of asthma severity. Yet, IL-13 gene polymorphism showed no significant association. Conclusion: Our findings underscore the complex interplay between genetic factors, demographic characteristics, and inflammation markers in determining asthma severity. It highlights the importance of personalized approaches to asthma management, considering individual genetic profiles to optimize management.