Tumor Necrotic Factor-Alpha (-308A/G, rs1800629) and Interleukin-13 (R130Q, rs20541) Gene Polymorphisms as Predictors of Severe Asthma in Pilot Cohort of Kuwaiti Population: Influence of Age, Nasal Polyps, Fractional Exhaled Nitric Oxide, and Blood Eosinophil Count.

Background: Genetic factors, along with sociodemographic characteristics, are believed to play a significant role in asthma pathogenesis.

Objective: This study investigated the role of Interleukin-13 (IL-13) and Tumor Necrosis Factor-alpha (TNF-α) gene polymorphisms, in conjunction with clinical characteristics, in predicting asthma severity.

Methods: A total of 214 asthma patients (98 mild, 116 severe) and 121 healthy individuals were genotyped using PCR-RFLP for IL-13 (R130Q, rs20541) and TNF-α (-308A/G, rs1800629) polymorphisms. Sociodemographic and clinical data were collected for statistical analysis.

Results: Compared to controls, the "Q" allele of the IL-13 gene increased the risk of mild asthma twofold but had no significant impact on severe asthma. Conversely, the "G" allele of the TNF-α gene increased the risk of mild asthma twofold and severe asthma threefold. Additionally, the TNF-α "GG" genotype was associated with a sixfold increased risk of asthma, while the "AG" genotype had a protective effect. In the comparison of mild versus severe asthma, the IL-13 "QQ" pattern was protective, while the TNF-α "GG" genotype increased the risk of severe asthma threefold, with "AG" being protective. Severe asthma patients were older, significantly associated with comorbid nasal polyposis (NP), had higher levels of FeNO and blood eosinophils. Logistic regression analysis identified the TNF-α "GG" genotype as independent significant predictor of asthma severity, whereas IL-13 polymorphism showed no association.

Conclusion: The TNF-α "GG" genotype emerges as a significant independent predictor of asthma severity, substantially increasing the risk of both mild and severe asthma. In contrast, IL-13 polymorphism, while associated with mild asthma, plays no significant role in severe asthma. Furthermore, severe asthma was strongly linked to older age, nasal polyposis, elevated FeNO levels, and blood eosinophils.