IL4 Gene Variants rs2243250 and rs2243248 and Their Association with Clinical Phenotypes of Severe Asthma in the Mexican Population: In Silico Functional Analysis and Regulatory Implications.

Severe asthma (SA) is a chronic respiratory disease characterized by clinical heterogeneity and poor therapeutic response. Variants in the IL4 gene, including rs2243250 and rs2243248, have been associated with asthma susceptibility and severity in different populations; however, their role in the Mexican population remains unclear. This study evaluated the association of IL4 promoter variants rs2243250 and rs2243248 with SA and related clinical characteristics in a Mexican population using genetic and in silico approaches. In total, 106 patients with SA and 180 healthy individuals were included. Genotyping was performed using allelic discrimination assays with TaqMan® probes, and associations between genotypes and clinical variables were assessed. No significant differences in allele or genotype frequencies were observed between groups. However, the rs2243250 TT genotype was associated with nocturnal symptoms (OR = 3.03, 95% CI = 1.31-7.00, p = 0.009) and increased use of rescue medication (OR = 3.16, 95% CI = 1.41-7.07, p = 0.005). The rs2243248 TG/GG genotypes were associated with epithelial allergy (p < 0.05). In silico analysis suggested a regulatory role for both variants. These findings suggest that IL4 variants may not influence overall disease risk but could modulate clinical features of asthma severity.