Influence of genetic variants and mRNA expression of interleukin IL17A gene in asthma susceptibility

Asthma is a chronic respiratory disease characterized by coughing, wheezing, shortness of breath, chest tightness, overproduction of mucus, and expiratory airflow limitation, which affects >300 million people worldwide. It is triggered by the dynamic interplay of genetic factors and environmental exposure. Th17 cells are an emerging subset of CD4+ T cells, which secrete IL-17A. This proinflammatory cytokine has recently been associated with asthma, autoimmune diseases, and inflammatory disorders. The present case-control study was focused on identifying the involvement of the IL-17A gene in asthma pathogenesis among 150 clinically diagnosed asthma patients and 150 healthy controls (HCs) of South Indian origin. To carry out the study, we aimed to screen the genetic variants of rs2275913G/A and rs8193036C/T and also estimated the serum cytokine levels of the IL-17A cytokine of recruited subjects. Further, we evaluated mRNA expression in selected subjects to correlate with the genetic variants. The results revealed that the mean IL-17A serum levels (161.6 ± 380.1 pg/ml vs. 86.75 ± 90.01 pg/ml) and IgE levels (257.7 ± 133.3 pg/ml vs. 311.2 ± 160.5 pg/ml) in asthma patients were significantly high as compared to healthy controls (p < 0.05). The ROC curves were constructed to compare the cytokine levels of asthma patients and HC, and the area under the curve (AUC) for IL-17A cytokine was 0.64, indicating that the test was satisfactory and significant (95 % CI: 0.575-0.709; p < 0.001). Genotyping of rs2275913G/A polymorphism indicated a 1.6-fold risk (95 % CI-1.02-2.56; p = 0.04) for asthma patients compared to healthy controls, whereas no significant association was observed for rs8193036C/T polymorphism with asthma susceptibility. Under genetic models, GA and AA models showed a protective effect against the disease for rs2275913G/A. In contrast, no statistically significant result was observed among the models of rs8193036C/T when adjusted with age and sex. The mRNA expression levels of the gene were statistically high in patients compared to the HCs, with a 1.8-fold change (p < 0.0001). We conclude that the results indicate IL-17A rs2275913G/A is likely to contribute to protection against the disease, while IL-17A rs8193036C/T shows no association with the disease. However, no correlation was identified in serum cytokine levels concerning genotypes. This comprehensive information in the present study might contribute to developing novel therapeutic strategies for treating inflammatory diseases like asthma. Further studies are warranted to understand the diverse functions of IL-17A concerning its longitudinal stability and its response to clinical interventions with large sample sizes in various ethnicities.